A Phase 2 Study of Durvalumab (MEDI4736) and Oleclumab (MEDI9447) in Multi-Cancer Populations With Correlation to Clinical, Molecular and Immunologic Parameters With DNA MethylaTION (DOMINATION)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- University Health Network, Toronto
- Locations
- 1
- Primary Endpoint
- Association between cfMeDIP and Response (defined as either complete response, partial response, or stable disease ≥ 4 cycles, as per RECIST 1.1. Association between cfMeDIP and Toxicity (defined as ≥ Grade 2 immune- adverse event (AE) as per CTCAE 5.0).
- Status
- Withdrawn
- Last Updated
- 5 years ago
Overview
Brief Summary
This is a Phase II, prospective, non-randomized, open-label trial involving cancer patients with known inflamed tumor types. Patients with previously treated advanced/metastatic non-small cell lung cancer or renal cell cancer will be recruited in near equal distribution. All patients must have documented response or prolonged stable disease to previous immunotherapy. At present, we plan to enrol 55 patients, to be treated with durvalumab and oleclumab. The regimen will consist of durvalumab 1500 mg given by vein every 4 weeks and oleclumab 3000 mg given by vein every 2 weeks x 4 doses then IV every 4 weeks till disease progression, withdrawal of subject consent, or another reason for discontinuation. Estimated total duration from time to first subjects consent to last subject's last visit is approximately 36 months.
Detailed Description
Study Hypotheses: 1. Circulating free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) can yield cancer type-agnostic predictive biomarker(s) of response and/or toxicity in subjects receiving this combination. 2. The combination of oleclumab (anti-cluster of differentiation \[CD\]73 monoclonal antibody) with durvalumab (anti programmed cell death ligand 1 \[PD-L1\]) will demonstrate adequate safety, tolerability, and antitumor activity in subjects with metastatic non-small-cell lung cancer (NSCLC) and renal cell cancer (RCC) previously treated with checkpoint inhibitors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥ 18 years at the time of screening or age of consent according to law
- •Life expectancy of at least 12 weeks
- •Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
- •ECOG 0 or 1
- •Weight ≥35kg
- •Subjects diagnosed with histologically or cytologically confirmed non small cell lung (NSCLC) or renal cell carcinoma (RCC)
- •Subjects must have at least 1 measurable lesion according to RECIST version 1.
- •Archival tumor formalin-fixed, paraffin-embedded (FFPE) specimens for correlative biomarker studies are required (1 H\&E and 15 unstained slides). Subjects with insufficient archived tumor samples are still eligible, pending discussion with the principal investigator on a case by case basis
- •Adequate organ and marrow function
- •Females of childbearing potential who are sexually active with a nonsterilized male partner must use at least one highly effective method of contraception from screening to 90 days after the final dose of study treatment
Exclusion Criteria
- •Receipt of any conventional or investigational anticancer therapy within 21 days or palliative radiotherapy within 14 days prior to the scheduled first dose of study treatment
- •Prior receipt of any agents targeting CD73, including patients treated with adenosine receptor antagonists, CD39 or CD73 inhibitors
- •Prior receipt of any innate immune agonists
- •Patients with NSCLC with known activating EGFR mutations or ALK translocations
- •Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
- •Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent
- •Subjects with a history of Grade 3 or greater thromboembolic events in the prior 12 months or thromboembolic event of any grade with ongoing symptoms
- •Subjects with prior history of myocardial infarction, transient ischemic attack, congestive heart failure ≥ Class 3 based on New York Heart Association Functional Classification or stroke within the past 3 months prior to the scheduled first dose of study treatment
- •Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment
- •HIV, Hep A, B, or C
Outcomes
Primary Outcomes
Association between cfMeDIP and Response (defined as either complete response, partial response, or stable disease ≥ 4 cycles, as per RECIST 1.1. Association between cfMeDIP and Toxicity (defined as ≥ Grade 2 immune- adverse event (AE) as per CTCAE 5.0).
Time Frame: 3 years
To identify cfMeDIP-seq-based predictive signature(s) that are correlated with specific outcome to durvalumab and oleclumab such as response/resistance or occurrence of toxicity in non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC)
Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame: 3 years
Disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame: 3 years
Duration of response (DoR)
Time Frame: 3 years
Secondary Outcomes
- Incidence of treatment-emergent adverse events (AEs)(3 years)
- Overall survival (OS) or progression-free survival (PFS)(3 years)