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

NCT03019003 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 16-425
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized, open-label, Phase Ib study to assess the safety and efficacy of a DNA methyltransferase inhibitor and immune checkpoint inhibitor(s) (durvalumab and/or tremelimumab) combination therapy in the treatment of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who have progressed during or after treatment with anti-PD-1, anti-PD-L1, or anti-CTLA-4 monotherapy for recurrent and/or metastatic disease. The clinical trial is studying drugs that can boost the participant's immune system against the cancer cells as a possible treatment for head and neck cancer. The study interventions involved in this study are:

• Oral Decitabine (ASTX 727) and 5' Azacytidine
• Durvalumab (MEDI4736) and Tremelimumab

Conditions

Head and Neck Cancer

Keywords

Head and Neck Cancer

Outcome Measures

Primary Outcomes (1)

• Change in Immune-based Biomarker Expression at Baseline and 2 Months

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

  2 months

Secondary Outcomes (1)

• Number of Participants With Dose Limiting Toxicity

  2 years

Study Arms (3)

Oral Decitabine and Durvalumab

EXPERIMENTAL

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.

Drug: Oral Decitabine; Drug: Durvalumab

5' Azacitidine 40 mg/m2 on Days 1-5, Durvalumab, and Tremelimumab

EXPERIMENTAL

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.

Drug: Durvalumab; Drug: 5' Azacitidine; Drug: Tremelimumab

5' Azacitidine 40 mg/m2 on Days 1-5 and 8-12, Durvalumab, and Tremelimumab

EXPERIMENTAL

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.

Drug: Durvalumab; Drug: 5' Azacitidine; Drug: Tremelimumab

Interventions

Oral Decitabine DRUG

DNA methyltransferase inhibitor

Also known as: ASTX 727

Oral Decitabine and Durvalumab

Durvalumab DRUG

anti-PD-L1

Also known as: MEDI4736

5' Azacitidine 40 mg/m2 on Days 1-5 and 8-12, Durvalumab, and Tremelimumab; 5' Azacitidine 40 mg/m2 on Days 1-5, Durvalumab, and Tremelimumab; Oral Decitabine and Durvalumab

5' Azacitidine DRUG

DNA methyltransferase inhibitor

Also known as: Vidaza

5' Azacitidine 40 mg/m2 on Days 1-5 and 8-12, Durvalumab, and Tremelimumab; 5' Azacitidine 40 mg/m2 on Days 1-5, Durvalumab, and Tremelimumab

Tremelimumab DRUG

anti-CTLA4

5' Azacitidine 40 mg/m2 on Days 1-5 and 8-12, Durvalumab, and Tremelimumab; 5' Azacitidine 40 mg/m2 on Days 1-5, Durvalumab, and Tremelimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and any locally-required authorization (e.g., HIPAA in the UEU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Age ≥ 18 years at time of study entry or adult male or female (according to age of majority as defined as ≥18 years)
• Histologically confirmed recurrent or metastatic SCCHN (oral cavity, oropharynx, hypopharynx, or larynx) not amenable to therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Patients who refuse radical resection are eligible.
• Tumor progression or recurrence during or after treatment with anti-PD1, anti-PDL1, anti-PDL2, anti-CTLA4, or other immune checkpoint inhibitor where the most recent dose was given within 3 months prior to study registration.
• Must give valid written consent to provide archival FFPE and/or newly acquired tumor tissue for the purpose of establishing baseline PD-L1 status as well as consent to provide on- and/or post-treatment tumor biopsy sample.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment
• Life expectancy of \> 6 months
• At least 1 lesion that can be accurately measured at baseline as \> 10 mm in the longest diameter (except lymph nodes which must have a short axis \>15 mm) with CT or MRI and that is suitable for accurate repeated measurements as per RECIST 1.1 guidelines.
• Adequate normal organ and marrow function as defined below (within 28 days prior to study registration):
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3)
• Platelet count ≥ 100 x 109/L (\>100,000 per mm3)
• Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.
• AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN
• Serum creatinine level \<1.5 x ULN and CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or staff at the study site)
• Histologically confirmed squamous cell carcinoma of any other primary anatomic location in the head and neck (eg. paranasal cavity) and non-squamous histologies (eg. nasopharynx or salivary gland)
• History of another primary malignancy except for:
• Malignancy treated with curative intent and with no known active disease ≥5 years before the first dose of study drug and of low potential risk for recurrence
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated carcinoma in situ without evidence of disease eg, cervical cancer in situ
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 21days prior to the first dose of study drug
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab (MEDI4736) or tremelimumab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
• Patients with Grade \> 2 neuropathy will be evaluated on a case-by-case basis and may be included after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with their assigned IP (eg, hearing loss) may be included after consultation with the Study Physician.
• Any prior Grade ≥3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \>Grade 1
• Abnormal coagulation parameters (PT \>15 seconds, PTT\>40 seconds, and/or INR \>1.5)
• Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis)

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• AstraZeneca: collaborator
• Astex Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (1)

• Qin T, Mattox AK, Campbell JS, Park JC, Shin KY, Li S, Sadow PM, Faquin WC, Micevic G, Daniels AJ, Haddad R, Garris CS, Pittet MJ, Mempel TR, ONeill A, Sartor MA, Pai SI. Epigenetic therapy sensitizes anti-PD-1 refractory head and neck cancers to immunotherapy rechallenge. J Clin Invest. 2025 Mar 17;135(6):e181671. doi: 10.1172/JCI181671.

  PMID: 40091844 RESULT

MeSH Terms

Conditions

Head and Neck Neoplasms

Interventions

Decitabine; durvalumab; Azacitidine; tremelimumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Sara Pai, MD, PhD
• Organization: Massachusetts General Hospital Cancer Center

sara.pai@mgh.harvard.edu

6178779118

Study Officials

• Sara Pai, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: January 6, 2017
• First Posted: January 12, 2017
• Study Start: March 20, 2017
• Primary Completion: September 24, 2024
• Study Completion: September 24, 2024
• Last Updated: September 16, 2025
• Results First Posted: September 16, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)