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)
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|ClinicalTrials.gov Identifier: NCT04262375|
Recruitment Status : Withdrawn (Overall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet.)
First Posted : February 10, 2020
Last Update Posted : November 17, 2020
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer Renal Cell Carcinoma||Biological: Durvalumab Biological: Oleclumab||Phase 2|
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||0 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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)|
|Estimated Study Start Date :||January 2021|
|Estimated Primary Completion Date :||January 2024|
|Estimated Study Completion Date :||January 2024|
Experimental: Durvalumab and Oleclumab
A single dose level for oleclumab and durvalumab will be used, comprising of Oleclumab 3000 mg IV Q2W for 4 doses, then Q4W AND Durvalumab 1500 mg IV Q4W
Durvalumab is a human immunoglobulin G (IgG)1 kappa monoclonal antibody directed against human PD-L1. Durvalumab selectively binds human PD-L1 with high affinity and blocks its ability to bind to PD-1 and cluster of differentiation (CD)80. The fragment crystallizable (Fc) domain of durvalumab contains a triple mutation in the constant domain of the IgG1 heavy chain that reduces binding to the complement component C1q and the Fc gamma receptors responsible for mediating antibody dependent cell mediated cytotoxicity.
Other Name: IMFINZI
Oleclumab is a human immunoglobulin G1 lambda monoclonal antibody (mAb) with a triple mutation in the heavy chain constant region for reduced effector function. Oleclumab selectively binds to cluster of differentiation 73 (ecto-5'-nucleotidase) (CD73) and inhibits CD73-associated ectonucleotidase activity, thereby inhibiting the CD73-mediated production of immunosuppressive adenosine. Extracellular adenosine contributes to the immunosuppressive effects of both regulatory T cells and myeloid derived suppressor cells, among others. This, in turn, leads to increased antitumor immunity.
- 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 ]
- Incidence of treatment-emergent adverse events (AEs) [ Time Frame: 3 years ]To assess the safety and tolerability of durvalumab and oleclumab in specific disease states in NSCLC and RCC
- Overall survival (OS) or progression-free survival (PFS) [ Time Frame: 3 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04262375
|Princess Margaret Cancer Centre|
|Toronto, Ontario, Canada, M5G 2M9|
|Principal Investigator:||Albiruni Razak, MD||Princess Margaret Cancer Centre|