Trial Outcomes & Findings for Durvalumab (MEDI4736) Plus Tremelimumab for Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin (NCT NCT03095274)

Last Updated: 2025-01-09

Results Overview

by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1, which is defined as the percentage of patients achieving complete response (CR), partial response (PR), or stable disease (SD) at month 9 after durvalumab plus tremelimumab was started. Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as \>=30% decrease in the sum of the longest diameter of target lesions; SD as no changes in target lesions (i.e. \<20% growth and \<30% decrease). CBR = CR + PR +SD. Some patients were not evaluable as they had no tumor assessments.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

126 participants

Primary outcome timeframe

9 months

Results posted on

2025-01-09

Participant Flow

The DUNE study had one unique arm receiving experimental treatment (druvalumab plus tremelimumab) The DUNE trial is a multicohort study with 4 groups that have different pathologies and prognosis. Therefore, baseline characteristics and efficacy results are reported separately for each cohort. Please review the information in study brief summary / detailed description for further details on each cohort.

Participant milestones

Participant milestones
Measure	Durvalumab+Tremelimumab Experiemntal: Durvalumab+Tremelimumab Durvalumab, 1500 mg Q4W (equivalent to 20 mg/kg Q4W) for 12 months in patients ≥ 30kg. Weight-based dosing should be used for patients \<30 kg: durvalumab 20 mg/kg. Tremelimumab 75 mg Q4W (equivalent to 1 mg/kg Q4W) for up to 4 doses/cycles in patients ≥ 30kg. Weight-based dosing should be used for patients \<30 kg: tremelimumab 1 mg/kg Q4.
Overall Study STARTED	123
Overall Study COMPLETED	123
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Durvalumab (MEDI4736) Plus Tremelimumab for Advanced Neuroendocrine Neoplasms of Gastroenteropancreatic or Lung Origin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 (Lung NETs) n=27 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 (G1-2 GI NENs) n=31 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 (panNETs) n=32 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 (G3 GEP NENs) n=33 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after	Total n=123 Participants Total of all reporting groups
Age, Continuous	62.32 years STANDARD_DEVIATION 11.40 • n=99 Participants	62.77 years STANDARD_DEVIATION 10.7 • n=107 Participants	65.06 years STANDARD_DEVIATION 11.29 • n=206 Participants	56.33 years STANDARD_DEVIATION 11.97 • n=7 Participants	61.54 years STANDARD_DEVIATION 11.56 • n=31 Participants
Sex: Female, Male Female	9 Participants n=99 Participants	13 Participants n=107 Participants	18 Participants n=206 Participants	11 Participants n=7 Participants	51 Participants n=31 Participants
Sex: Female, Male Male	18 Participants n=99 Participants	18 Participants n=107 Participants	14 Participants n=206 Participants	22 Participants n=7 Participants	72 Participants n=31 Participants
Race/Ethnicity, Customized Caucasic	26 Participants n=99 Participants	31 Participants n=107 Participants	32 Participants n=206 Participants	33 Participants n=7 Participants	122 Participants n=31 Participants
Race/Ethnicity, Customized African	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants

PRIMARY outcome

Timeframe: 9 months

Outcome measures

Outcome measures
Measure	Cohort 1 n=25 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 n=29 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=29 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=29 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Clinical Benefit Rate (CBR) SD	6 Participants	11 Participants	6 Participants	0 Participants
Clinical Benefit Rate (CBR) CR	0 Participants	0 Participants	0 Participants	1 Participants
Clinical Benefit Rate (CBR) PR	1 Participants	0 Participants	2 Participants	1 Participants
Clinical Benefit Rate (CBR) PD	18 Participants	16 Participants	20 Participants	27 Participants
Clinical Benefit Rate (CBR) Follow-up less than 9m (without previous PD/Death)	0 Participants	2 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Throughout the study period. Each patients has been followed approximately 24 months, up to 30 months.

Time between start of treatment and death. Here we report the median time to death from any cause, estimated by Kaplan Meier method. The times reported in here are the median time to event estimated by Kaplan Meier and that is why the number of months might be higher or lower than the overall and patient-specific follow-up.

Outcome measures

Outcome measures
Measure	Cohort 1 n=19 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 n=21 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=23 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=11 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Overall Survival	NA months median not reached with the current follow.up. It is not feasible to calculate the confidence interval of a unknown (not reached) median	29.49 months Interval 21.86 to 37.11	24.83 months Interval 15.33 to 34.32	7.04 months Interval 4.08 to 10.01

SECONDARY outcome

Timeframe: 9 months

by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria. dAssessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as \>=30% decrease in the sum of the longest diameter of target lesions. ORR = CR + PR

Outcome measures

Outcome measures
Measure	Cohort 1 n=27 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 n=31 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=32 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=33 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Overall Response Rate CR or PR	3 Participants	0 Participants	2 Participants	3 Participants
Overall Response Rate No response	24 Participants	31 Participants	30 Participants	30 Participants

SECONDARY outcome

Timeframe: Throughout the study period, approximately 24 months

Population: No patient had a response to treatment (not CR, not PR)

by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria. Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as \>=30% decrease in the sum of the longest diameter of target lesions. Response = CR + PR

Outcome measures

Outcome measures
Measure	Cohort 1 n=3 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=2 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=3 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Duration of Response	2.98 months Interval 2.68 to 15.5	—	16.31 months Interval 10.64 to 21.98	10.08 months Interval 3.9 to 24.26

SECONDARY outcome

Timeframe: Throughout the study period, approximately 24 months

by immune-related Response Evaluation Criteria In Solid Tumors (irRECIST) criteria

Outcome measures

Outcome measures
Measure	Cohort 1 n=24 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 n=27 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=29 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=33 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Progression Free Survival	5.55 months Interval 4.94 to 6.17	5.79 months Interval 3.12 to 8.45	5.52 months Interval 2.38 to 8.66	2.41 months Interval 2.08 to 2.75

SECONDARY outcome

Timeframe: 9 months

Population: In the following table, the most frequent toxicities are reported (toxicities with frequency ≥10%)

Based on subjects who experienced toxicities as defined by CTCAE, v4.0 The attribution to drug, time-of-onset, duration of the event, its resolution, and any concomitant medications.

Outcome measures

Outcome measures
Measure	Cohort 1 n=27 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 n=31 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=32 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=33 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Safety - Toxicities as Defined by CTCAE, v4.0 Fatigue Related · no	19 Participants	16 Participants	12 Participants	21 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Fatigue Related · yes	8 Participants	15 Participants	20 Participants	12 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Diarrhea Related · no	16 Participants	19 Participants	21 Participants	27 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Diarrhea Related · yes	11 Participants	12 Participants	11 Participants	6 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Pruritus Related · no	23 Participants	21 Participants	22 Participants	28 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Pruritus Related · yes	4 Participants	10 Participants	10 Participants	5 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Nausea Related · no	26 Participants	25 Participants	24 Participants	30 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Nausea Related · yes	1 Participants	6 Participants	8 Participants	3 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Skin and subcutaneous tissue disorders - Other, specify Related · no	24 Participants	28 Participants	27 Participants	32 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Skin and subcutaneous tissue disorders - Other, specify Related · yes	3 Participants	3 Participants	5 Participants	1 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Hypothyroidism Related · no	25 Participants	26 Participants	30 Participants	29 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Hypothyroidism Related · yes	2 Participants	5 Participants	2 Participants	4 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Vomiting Related · no	25 Participants	28 Participants	29 Participants	29 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Vomiting Related · yes	2 Participants	3 Participants	3 Participants	4 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Arthralgia Related · no	25 Participants	27 Participants	26 Participants	32 Participants
Safety - Toxicities as Defined by CTCAE, v4.0 Arthralgia Related · yes	2 Participants	4 Participants	6 Participants	1 Participants

SECONDARY outcome

Timeframe: 12 months

by irRECIST criteria, at 6, 9 and 12 months after start of study treatment. Assessed by Computed tomography scan (CT) or magnetic resonance imaging (MRI) CR is defined as disappearance of all target lesions; PR as \>=30% decrease in the sum of the longest diameter of target lesions. ORR = CR + PR

Outcome measures

Outcome measures
Measure	Cohort 1 n=27 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 n=31 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=32 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=33 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Response Status CR or PR	1 Participants	0 Participants	1 Participants	2 Participants
Response Status No response	26 Participants	31 Participants	31 Participants	31 Participants

SECONDARY outcome

Timeframe: 9 months

Outcome measures

Outcome measures
Measure	Cohort 1 n=27 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 n=31 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=32 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=33 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Response Status CR or PR	1 Participants	0 Participants	2 Participants	2 Participants
Response Status No response	26 Participants	31 Participants	30 Participants	31 Participants

SECONDARY outcome

Timeframe: 6 months

Outcome measures

Outcome measures
Measure	Cohort 1 n=27 Participants Well-moderately differentiated lung neuroendocrine tumors (classically known as typical and atypical carcinoids) after progression to somatostatin analogs and one prior targeted therapy or chemotherapy.	Cohort 2 n=31 Participants Well-moderately differentiated G1/G2 (WHO grade 1 and 2) gastrointestinal neuroendocrine tumors after progression to somatostatin analogs and one targeted therapy (prior targeted therapy could be everolimus or a multikinase inhibitor). Prior therapies with interferon alpha-2b or radionucleotide therapy are allowed.	Cohort 3 n=32 Participants Cohort 3 : Well-moderately differentiated neuroendocrine tumors G1/G2 (WHO grade 1 and 2) from pancreatic origin after progression to standard therapies (chemotherapy, somatostatin analogs and target therapy); patients must be treated with at least two prior systemic treatment lines and a maximum of four previous treatment lines.	Cohort 4 n=33 Participants Cohort 4 : Neuroendocrine neoplasms (WHO grade 3) of gastroenteropancreatic origin or unknown primary site (excluding lung primary tumors), patients will be treated in second line only, after
Response Status No response	26 Participants	31 Participants	30 Participants	31 Participants
Response Status CR or PR	1 Participants	0 Participants	2 Participants	2 Participants

Adverse Events

Cohort 1

Serious events: 10 serious events

Other events: 27 other events

Deaths: 9 deaths

Cohort 2

Serious events: 15 serious events

Other events: 31 other events

Deaths: 17 deaths

Cohort 3

Serious events: 16 serious events

Other events: 32 other events

Deaths: 21 deaths

Cohort 4

Serious events: 22 serious events

Other events: 33 other events

Deaths: 30 deaths

Serious adverse events

Other adverse events

Additional Information

A responsibility person designate by sponsor

MFAR

Phone: 934344412

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place