Trial Outcomes & Findings for Neoadjuvant Dabrafenib, Trametinib and/or Pembrolizumab in BRAF Mutant Resectable Stage III Melanoma (NCT NCT02858921)

Results Overview

Proportion of patients with a complete absence of residual melanoma cells in the planned resected tumour site(s) at week 6 surgery.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

From baseline to 6 weeks

Results posted on

2026-08-24

Participant Flow

Screened but found ineligible and excluded prior to randomisation n= 3

Participant milestones

Participant milestones
Measure	Pembrolizumab ONLY Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Overall Study STARTED	20	20	20
Overall Study COMPLETED	20	20	20
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Some patients had more than one lymph node site involved

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: From baseline to 6 weeks

Population: A total of 3 patients did not proceed to surgery due to distant disease progression and the pathological response was not evaluable.

Proportion of patients with a complete absence of residual melanoma cells in the planned resected tumour site(s) at week 6 surgery.

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=20 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Pathological Response Rate Complete Pathological Response	6 Participants	3 Participants	10 Participants
Pathological Response Rate Near Pathological Response	2 Participants	3 Participants	1 Participants
Pathological Response Rate Partial Pathological Response	3 Participants	4 Participants	5 Participants
Pathological Response Rate No Pathological Response	7 Participants	10 Participants	3 Participants
Pathological Response Rate Not Evaluable	2 Participants	0 Participants	1 Participants

SECONDARY outcome

Timeframe: From baseline to 6 weeks

Proportion of patients with complete and partial responses at 6 weeks compared to baseline per RECIST guidelines for each treatment arm.

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=20 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Objective Clinical (RECIST) Response Rate Stable Disease	9 Participants	10 Participants	5 Participants
Objective Clinical (RECIST) Response Rate Disease Progression	5 Participants	1 Participants	1 Participants
Objective Clinical (RECIST) Response Rate Partial Response	4 Participants	9 Participants	7 Participants
Objective Clinical (RECIST) Response Rate Complete Response	2 Participants	0 Participants	7 Participants

SECONDARY outcome

Timeframe: 12 months

Population: 12 month relapse free survival rate

The 12 month relapse free survival rate. Proportion of patients who have not recurred % (95% CI)

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=18 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=19 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
12 Month Relapse Free Survival	89 % of participants Interval 75.0 to 100.0	80 % of participants Interval 60.0 to 100.0	84 % of participants Interval 69.0 to 100.0

SECONDARY outcome

Timeframe: 24 months

Population: 24 month relapse free survival rate

Proportion of patients who are recurrence free at 24 months

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=5 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=9 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=6 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
24 Month Relapse Free Survival	66 % of patients Interval 45.0 to 96.0	80 % of patients Interval 64.0 to 100.0	75 % of patients Interval 55.0 to 100.0

SECONDARY outcome

Timeframe: 12 months

Population: 12 month overall survivall

The proportion of patients who are alive at 12 months from the time of study entry

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=20 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=18 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=18 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
12 Month Overall Survival Rate	94 % of participants Interval 84.0 to 100.0	95 % of participants Interval 85.0 to 100.0	95 % of participants Interval 85.0 to 100.0

SECONDARY outcome

Timeframe: 24 months

Population: 24 month overall survival rate

The proportion of patients who are alive at 24 months from the time of study entry

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=9 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=10 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=8 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
24 Month Overall Survival Rate	76 % of patients Interval 55.0 to 100.0	89 % of patients Interval 75.0 to 100.0	95 % of patients Interval 85.0 to 100.0

SECONDARY outcome

Timeframe: 6 weeks

Population: The number of participants who had surgey at week 6.

The number of patients who develop a post operative infection of the surgical wound requiring intravenous antibiotics and/or wound drainage (Common Terminology Criteria for Adverse Events (CTCAE) v5.0 - Grade 3 or over

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=18 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=19 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Incidence of Post Operative Infection	2 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: 6 weeks

Population: The number of participants who had surgery at week 6.

The number of patients who developed a seroma at the surgical site that required any invasive intervention (Common Terminology Criteria for Adverse Events \[CTCAE v5.0\] - Grade 3)

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=18 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=19 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Incidence of Post Operative Seroma Formation	2 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and 6 weeks

Population: Results are for patients who underwent surgery and had completed surgical assessments.

The change, if any, in the surgeon's assessment of 'operability' from baseline opinion (based on clinical and imaging examination) to time of operation

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=17 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=19 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=17 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Comparison of Surgeon's Opinion of Operability Evaluated at Baseline to Time of Surgery Easier resectability	2 Participants	4 Participants	8 Participants
Comparison of Surgeon's Opinion of Operability Evaluated at Baseline to Time of Surgery Similar resectability	10 Participants	13 Participants	6 Participants
Comparison of Surgeon's Opinion of Operability Evaluated at Baseline to Time of Surgery Harder Resectability	5 Participants	2 Participants	3 Participants

SECONDARY outcome

Timeframe: 52 weeks

The number of patients experiencing study treatment-related adverse events of all Common Terminology Criteria for Adverse Events (CTCAE version 5.0) grades.

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=20 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Incidence of Any Study Treatment-related Adverse Events	17 Participants	19 Participants	20 Participants

SECONDARY outcome

Timeframe: 52 weeks

The number of patients with treatment-related adverse events of grade 3 or 4 using Common Terminology Criteria for Adverse Events (CTCAE version 5.0 ) grades

Outcome measures

Outcome measures
Measure	Pembrolizumab ONLY n=20 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
Incidence of Any Grade 3/4 Treatment Related Adverse Events	1 Participants	5 Participants	11 Participants

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 6

The effects of study treatment on the baseline function of RNA expression in tumour tissue prior to surgery

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 6

The effects of study treatment on the number and type of white cells in the blood

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Week 1, Week 2, Week 6

The levels of melanoma DNA that is circulating in the blood stream and the changes during study treatment

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks

The number of patients (and the number of episodes) who have a bleed from the post operative surgical wound that requires a blood transfusion or return to theatre to stop the bleeding

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 6 weeks

The number of days that a wound drain remains in situ from the time of surgery

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

The activity of melanoma tissue assessed by the uptake of fludeoxyglucose (18F) in tumour cells viewed using positron emission tomography (PET) and how well this corresponds to the findings from the pathological examination of completely excised tumour tissue

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 weeks

The activity of melanoma tissue assessed by the uptake of fludeoxyglucose (18F) in tumour cells viewed using positron emission tomography (PET) and how well this corresponds to the assessment of tumour size and extent using computed tomography and magnetic resonance imaging scans

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 6 weeks

he findings from the pathological examination of completely excised tumour tissue and how well this corresponds to the assessment of tumour size and extent using computed tomography and magnetic resonance imaging scans

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 52 weeks

The activity of recurrent melanoma tissue assessed by the uptake of fludeoxyglucose (18F) in tumour cells viewed using positron emission tomography (PET) and how well this corresponds to the assessment of tumour size and extent using computed tomography and magnetic resonance imaging scans

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 6 and 52

The application of two different criterion to establish the tumour burden as assessed with computed tomorgraphy and magnetic resonanse imaging

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 6, week 24, at relapse if this occurs within 5 years from study entry

Characterisation of the bacterial diversity and composition in stool samples at baseline, prior to surgery at week 6, week 24 and at relapse.

Outcome measures

Outcome data not reported

Adverse Events

Sequential D + T, THEN Pembrolizumab

Serious events: 6 serious events

Other events: 19 other events

Deaths: 3 deaths

Concurrent D + T AND Pembrolizumab

Serious events: 11 serious events

Other events: 20 other events

Deaths: 2 deaths

Pembrolizumab ONLY

Serious events: 1 serious events

Other events: 17 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Sequential D + T, THEN Pembrolizumab n=20 participants at risk Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=20 participants at risk Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Pembrolizumab ONLY n=20 participants at risk Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
General disorders Pyrexia	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	15.0% 3/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Gastrointestinal disorders Diarrhoea	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Nervous system disorders Guillain-Barre syndrome	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Musculoskeletal and connective tissue disorders Arthritis	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Investigations ALT increased	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Investigations AST increased	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Investigations GGT increased	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Investigations Lipase increased	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Investigations WCC decreased	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Hepatobiliary disorders Hepatitis	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Hepatobiliary disorders Drug induced liver injury	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Infections and infestations Wounbd infection	5.0% 1/20 • Number of events 1 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • Number of events 1 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.

Other adverse events

Other adverse events
Measure	Sequential D + T, THEN Pembrolizumab n=20 participants at risk Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=20 participants at risk Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Pembrolizumab ONLY n=20 participants at risk Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
General disorders Pyrexia	20.0% 4/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	85.0% 17/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
General disorders Fatigue	70.0% 14/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	70.0% 14/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	65.0% 13/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
General disorders Chills	20.0% 4/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	50.0% 10/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
General disorders Influenza type illness	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Skin and subcutaneous tissue disorders Rash	35.0% 7/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	35.0% 7/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	45.0% 9/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Skin and subcutaneous tissue disorders Pruritis	40.0% 8/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	35.0% 7/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Skin and subcutaneous tissue disorders Viiligo	15.0% 3/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	25.0% 5/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Skin and subcutaneous tissue disorders Hyperhydrosis	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Skin and subcutaneous tissue disorders Erythema	5.0% 1/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Gastrointestinal disorders Nausea	30.0% 6/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	40.0% 8/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	15.0% 3/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Injury, poisoning and procedural complications Seroma	10.0% 2/20 • Number of events 2 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • Number of events 2 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.
Injury, poisoning and procedural complications Wound infection	10.0% 2/20 • Number of events 2 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	0.00% 0/20 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.	10.0% 2/20 • Number of events 2 • All cause mortality data collected over 24 months All serious adverse event data collected over 52 weeks Adverse event data collected over 52 weeks All cause serious adverse events are reported per clinicaltrials.gov definition. All adverse events were recorded, whether or not considered related of to the participant's participation in the research. The secondary outcome data of "Incidence of any treatment-emergent adverse events" have been reported. Adverse event data collection included: at regular investigator assessments, regular laboratory testing, participant self-reporting.

Additional Information

Investigator Initiated Clinical Trials Operatons Manager

Melanoma Institute Australia

Phone: +61 2 9911 7296

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pembrolizumab ONLY n=20 Participants Pembrolizumab 200mg intravenously once every 3 weeks alone for 52 weeks. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Sequential D + T, THEN Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day for 1 week, then followed by treatment with Pembrolizumab 2mg/kg delivered intravenously at weeks 1, 3, and 6, then once every 3 weeks from week 6 for 46 weeks. Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Concurrent D + T AND Pembrolizumab n=20 Participants Dabrafenib 150mg orally twice a day + Trametinib 2mg orally once a day + Pembrolizumab 200mg intravenously once every 3 weeks for 6 weeks, the Pembrolizumab alone for 46 weeks Dabrafenib: Dabrafenib, a 4-(3-aminosulfonylphenyl)-5-(pyrimidine-3-yl) thiazole, is a potent and selective inhibitor of B-RAF kinase activity with a mode of action consistent with adenosine triphosphate (ATP)-competitive inhibition, and is approved as monotherapy in BRAF V600E-mutant advanced/metastatic melanoma. Trametinib: Trametinib, a pyrido - pyrimidine derivative, is a potent and highly selective allosteric non-competitive inhibitor of MEK1/MEK2 activation and kinase activity has been approved as monotherapy in BRAF (V600E)-mutant and BRAF (V600K)-mutant melanoma. Pembrolizumab: Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the IgG4/kappa isotype designed to directly block the interaction between PD-1 and its ligands, PD-L1 and PD-L2.	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=20 Participants • Some patients had more than one lymph node site involved	0 Participants n=20 Participants • Some patients had more than one lymph node site involved	0 Participants n=20 Participants • Some patients had more than one lymph node site involved	0 Participants n=60 Participants • Some patients had more than one lymph node site involved
Age, Categorical Between 18 and 65 years	20 Participants n=20 Participants • Some patients had more than one lymph node site involved	20 Participants n=20 Participants • Some patients had more than one lymph node site involved	20 Participants n=20 Participants • Some patients had more than one lymph node site involved	60 Participants n=60 Participants • Some patients had more than one lymph node site involved
Age, Categorical >=65 years	0 Participants n=20 Participants • Some patients had more than one lymph node site involved	0 Participants n=20 Participants • Some patients had more than one lymph node site involved	0 Participants n=20 Participants • Some patients had more than one lymph node site involved	0 Participants n=60 Participants • Some patients had more than one lymph node site involved
Age, Continuous	56 Years n=20 Participants	50 Years n=20 Participants	53 Years n=20 Participants	53 Years n=60 Participants
Sex: Female, Male Female	8 Participants n=20 Participants	8 Participants n=20 Participants	9 Participants n=20 Participants	25 Participants n=60 Participants
Sex: Female, Male Male	12 Participants n=20 Participants	12 Participants n=20 Participants	11 Participants n=20 Participants	35 Participants n=60 Participants
Race and Ethnicity Not Collected	—	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Australia	20 Participants n=20 Participants	20 Participants n=20 Participants	20 Participants n=20 Participants	60 Participants n=60 Participants
ECOG ECOG status 0	20 Participants n=20 Participants	20 Participants n=20 Participants	19 Participants n=20 Participants	59 Participants n=60 Participants
ECOG ECOG Status 1	0 Participants n=20 Participants	0 Participants n=20 Participants	1 Participants n=20 Participants	1 Participants n=60 Participants
BRAF Mutation Type V600E	16 Participants n=20 Participants	16 Participants n=20 Participants	17 Participants n=20 Participants	49 Participants n=60 Participants
AJCC N Stage AJCC Stage N1b (1 clinically detected lymph node metastasis)	13 Participants n=20 Participants	11 Participants n=20 Participants	14 Participants n=20 Participants	38 Participants n=60 Participants
AJCC N Stage AJCC Stage N2b (2-3 clinically detected lymph node metastases)	3 Participants n=20 Participants	6 Participants n=20 Participants	3 Participants n=20 Participants	12 Participants n=60 Participants
AJCC N Stage AJCC Stage N3b (>3 lymph nodes metastases, 1 or more clinically detected or matted node)	4 Participants n=20 Participants	3 Participants n=20 Participants	3 Participants n=20 Participants	10 Participants n=60 Participants
BRAF Mutation Type V600R	1 Participants n=20 Participants	0 Participants n=20 Participants	1 Participants n=20 Participants	2 Participants n=60 Participants
BRAF Mutation Type V600K	3 Participants n=20 Participants	4 Participants n=20 Participants	2 Participants n=20 Participants	9 Participants n=60 Participants
Lymph node sites stratified by treatment group Neck	7 Participants n=20 Participants	0 Participants n=20 Participants	4 Participants n=20 Participants	11 Participants n=60 Participants
Lymph node sites stratified by treatment group Parotid	4 Participants n=20 Participants	2 Participants n=20 Participants	1 Participants n=20 Participants	7 Participants n=60 Participants
Lymph node sites stratified by treatment group Supraclavian	0 Participants n=20 Participants	1 Participants n=20 Participants	0 Participants n=20 Participants	1 Participants n=60 Participants
Lymph node sites stratified by treatment group Axilla	7 Participants n=20 Participants	9 Participants n=20 Participants	10 Participants n=20 Participants	26 Participants n=60 Participants
Lymph node sites stratified by treatment group Iliac	0 Participants n=20 Participants	1 Participants n=20 Participants	1 Participants n=20 Participants	2 Participants n=60 Participants
Lymph node sites stratified by treatment group Inguinal	5 Participants n=20 Participants	8 Participants n=20 Participants	4 Participants n=20 Participants	17 Participants n=60 Participants