Trial Outcomes & Findings for Oral Decitabine (ASTX727) and Durvalumab in Recurrent and/or Metastatic Head and Neck Cancer Patients (NCT NCT03019003)

NCT ID: NCT03019003

Last Updated: 2025-09-16

Results Overview

Greater than 2-fold change in immune-based biomarker expression within the tumor microenvironment

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

13 participants

Primary outcome timeframe

2 months

Results posted on

2025-09-16

Participant Flow

Participant milestones

Participant milestones
Measure	Low Dose 5'Aza (40 mg/m^2) for Days 1-5 + Durvalumab + Tremelimumab Low dose 5'aza (40 mg/m\^2) administered subcutaneously daily for 5 days + Durvalumab + Tremelimumab	Low Dose 5'Aza (40 mg/m^2) for Days 1-5 and 8-12 + Durvalumab 1500 mg Q4W + Tremelimumab 75 mg Q4W Low dose 5'aza (40 mg/m\^2) administered subcutaneously daily for 10 days + Durvalumab + Tremelimumab	Oral Decitabine 35 mg QD Days 1-3 and Durvalumab 1500 mg Q4W Oral Decitabine will be administered orally daily for Days 1-3 + Durvalumab 1500 mg Q4W
Overall Study STARTED	7	5	1
Overall Study COMPLETED	7	5	1
Overall Study NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Oral Decitabine (ASTX727) and Durvalumab in Recurrent and/or Metastatic Head and Neck Cancer Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	5' Azacytidine (40 mg/m^2) Days 1-5 + Durvalumab + Tremelimumab n=7 Participants Low Dose 5'aza (40 mg/m\^2) SC daily will be administered alone in Cycle 1 and the combination of 5'aza, durvalumab, and tremelimumab therapy will be given in Cycles 2-12. 5'aza: DNA Methyltransferase Inhibitor Durvalumab: anti-PD-L1 Tremelimumab: anti-CTLA4	5' Azacytidine (40 mg/m^2) Days 1-5 and 8-12 + Durvalumab + Tremelimumab n=5 Participants Low Dose 5'aza (40 mg/m\^2) SC daily will be administered alone in Cycle 1 and the combination of 5'aza, durvalumab, and tremelimumab therapy will be given in Cycles 2-12. 5'aza: DNA Methyltransferase Inhibitor Durvalumab: anti-PD-L1 Tremelimumab: anti-CTLA4	Oral Decitabine Days 1-3 + Durvalumab n=1 Participants Oral Decitabine (35 mg) will be administered alone in Cycle 1 and the combination of decitabine and durvalumab will be given in Cycles 2-12. 5'aza: DNA Methyltransferase Inhibitor Durvalumab: anti-PD-L1	Total n=13 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=99 Participants	3 Participants n=107 Participants	0 Participants n=206 Participants	6 Participants n=7 Participants
Age, Categorical >=65 years	4 Participants n=99 Participants	2 Participants n=107 Participants	1 Participants n=206 Participants	7 Participants n=7 Participants
Age, Continuous	62.9 years STANDARD_DEVIATION 6.5 • n=99 Participants	61.4 years STANDARD_DEVIATION 9.6 • n=107 Participants	67.1 years STANDARD_DEVIATION 0 • n=206 Participants	65.5 years STANDARD_DEVIATION 7.4 • n=7 Participants
Sex: Female, Male Female	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Sex: Female, Male Male	7 Participants n=99 Participants	4 Participants n=107 Participants	1 Participants n=206 Participants	12 Participants n=7 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=99 Participants	5 Participants n=107 Participants	1 Participants n=206 Participants	12 Participants n=7 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	1 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Race (NIH/OMB) White	6 Participants n=99 Participants	4 Participants n=107 Participants	1 Participants n=206 Participants	11 Participants n=7 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants
Region of Enrollment United States	7 participants n=99 Participants	5 participants n=107 Participants	1 participants n=206 Participants	13 participants n=7 Participants

PRIMARY outcome

Timeframe: 2 months

Greater than 2-fold change in immune-based biomarker expression within the tumor microenvironment

Outcome measures

Outcome measures
Measure	Oral Decitabine and Durvalumab n=1 Participants Oral decitabine (ASTX 727) will be administered alone in Cycle 1 and the combination of oral decitabine and durvalumab therapy will be given in Cycles 2-12. Oral Decitabine: DNA methyltransferase inhibitor Durvalumab: anti-PD-L1	5' Azacitidine 40 mg/m^2 on Days 1-5 and 8-12, Durvalumab, and Tremelimumab n=5 Participants 5' Azacitidine will be administered alone in Cycle 1 and the combination of 5' Azacitidine, durvalumab, and tremelimumab therapy will be given in Cycles 2-12. Durvalumab: anti-PD-L1 5' Azacitidine: DNA methyltransferase inhibitor Tremelimumab: anti-CTLA4	5' Azacitidine 40 mg/m^2 on Days 1-5, Durvalumab, and Tremelimumab n=7 Participants 5' Azacitidine will be administered alone in Cycle 1 and the combination of 5' Azacitidine, durvalumab, and tremelimumab therapy will be given in Cycles 2-12. Durvalumab: anti-PD-L1 5' Azacitidine: DNA methyltransferase inhibitor Tremelimumab: anti-CTLA4
Change in Immune-based Biomarker Expression at Baseline and 2 Months	0 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 years

Adverse events were reported using Common Terminology Criteria for Adverse Events (CTCAE) v4.3.

Outcome measures

Outcome measures
Measure	Oral Decitabine and Durvalumab n=1 Participants Oral decitabine (ASTX 727) will be administered alone in Cycle 1 and the combination of oral decitabine and durvalumab therapy will be given in Cycles 2-12. Oral Decitabine: DNA methyltransferase inhibitor Durvalumab: anti-PD-L1	5' Azacitidine 40 mg/m^2 on Days 1-5 and 8-12, Durvalumab, and Tremelimumab n=7 Participants 5' Azacitidine will be administered alone in Cycle 1 and the combination of 5' Azacitidine, durvalumab, and tremelimumab therapy will be given in Cycles 2-12. Durvalumab: anti-PD-L1 5' Azacitidine: DNA methyltransferase inhibitor Tremelimumab: anti-CTLA4	5' Azacitidine 40 mg/m^2 on Days 1-5, Durvalumab, and Tremelimumab n=5 Participants 5' Azacitidine will be administered alone in Cycle 1 and the combination of 5' Azacitidine, durvalumab, and tremelimumab therapy will be given in Cycles 2-12. Durvalumab: anti-PD-L1 5' Azacitidine: DNA methyltransferase inhibitor Tremelimumab: anti-CTLA4
Number of Participants With Dose Limiting Toxicity	0 Participants	1 Participants	0 Participants

Adverse Events

Low Dose 5'Aza (40 mg/m^2) for Days 1-5 + Durvalumab + Tremelimumab

Serious events: 1 serious events

Other events: 7 other events

Deaths: 7 deaths

Low Dose 5'Aza (40 mg/m^2) for Days 1-5 and 8-12 + Durvalumab 1500 mg Q4W + Tremelimumab 75 mg Q4W

Serious events: 4 serious events

Other events: 2 other events

Deaths: 4 deaths

Oral Decitabine 35 mg QD Days 1-3 and Durvalumab 1500 mg Q4W

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Low Dose 5'Aza (40 mg/m^2) for Days 1-5 + Durvalumab + Tremelimumab n=7 participants at risk Low dose 5'aza (40 mg/m\^2) administered subcutaneously daily for 5 days + Durvalumab + Tremelimumab	Low Dose 5'Aza (40 mg/m^2) for Days 1-5 and 8-12 + Durvalumab 1500 mg Q4W + Tremelimumab 75 mg Q4W n=5 participants at risk Low dose 5'aza (40 mg/m\^2) administered subcutaneously daily for 10 days + Durvalumab + Tremelimumab	Oral Decitabine 35 mg QD Days 1-3 and Durvalumab 1500 mg Q4W n=1 participants at risk Oral Decitabine will be administered orally daily for Days 1-3 + Durvalumab 1500 mg Q4W
Nervous system disorders Stroke	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Injury, poisoning and procedural complications Fall	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Investigations Neutropenia	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Gastrointestinal disorders oral hemorrhage	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
General disorders Fever	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Musculoskeletal and connective tissue disorders Back Pain	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	100.0% 1/1 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.

Other adverse events

Additional Information

Dr. Sara Pai, MD, PhD

Massachusetts General Hospital Cancer Center

Phone: 6178779118

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Low Dose 5'Aza (40 mg/m^2) for Days 1-5 + Durvalumab + Tremelimumab n=7 participants at risk Low dose 5'aza (40 mg/m\^2) administered subcutaneously daily for 5 days + Durvalumab + Tremelimumab	Low Dose 5'Aza (40 mg/m^2) for Days 1-5 and 8-12 + Durvalumab 1500 mg Q4W + Tremelimumab 75 mg Q4W n=5 participants at risk Low dose 5'aza (40 mg/m\^2) administered subcutaneously daily for 10 days + Durvalumab + Tremelimumab	Oral Decitabine 35 mg QD Days 1-3 and Durvalumab 1500 mg Q4W n=1 participants at risk Oral Decitabine will be administered orally daily for Days 1-3 + Durvalumab 1500 mg Q4W
Gastrointestinal disorders Constipation	28.6% 2/7 • Number of events 2 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Metabolism and nutrition disorders hypomagnesmia	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Investigations Weight Loss	28.6% 2/7 • Number of events 2 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Reproductive system and breast disorders Pelvic Pain	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Investigations Investigations - Other	57.1% 4/7 • Number of events 4 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Investigations Alkaline phosphatase increase	14.3% 1/7 • Number of events 2 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Metabolism and nutrition disorders Anorexia	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Musculoskeletal and connective tissue disorders Arthralgia	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Investigations Aspartate aminotrasnferase increased	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Gastrointestinal disorders diarrhea	14.3% 1/7 • Number of events 2 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
General disorders fatigue	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Investigations GGT increased	14.3% 1/7 • Number of events 2 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Renal and urinary disorders Hematuria	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Metabolism and nutrition disorders Hyperglycemia	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Metabolism and nutrition disorders Hypernatremia	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Metabolism and nutrition disorders Hypomagnesemia	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Metabolism and nutrition disorders Hyponatremia	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Gastrointestinal disorders Lip Pain	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Infections and infestations Lung infection	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Gastrointestinal disorders Nausea	42.9% 3/7 • Number of events 3 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Skin and subcutaneous tissue disorders Pruritus	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Gastrointestinal disorders Toothache	14.3% 1/7 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Blood and lymphatic system disorders Febrile Neutropenia	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 2 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Gastrointestinal disorders Salivary duct inflammation	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Renal and urinary disorders Urinary retention	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Cardiac disorders Ventricular Arrhythmia	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	20.0% 1/5 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/1 • Adverse events were monitored in participants for up to 2 years.
Investigations Neutrophil count decreased	0.00% 0/7 • Adverse events were monitored in participants for up to 2 years.	0.00% 0/5 • Adverse events were monitored in participants for up to 2 years.	100.0% 1/1 • Number of events 1 • Adverse events were monitored in participants for up to 2 years.