Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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Recruitment Status : Withdrawn (Overall clinical activity (ORR) for oleclumab + durvalumab is minimal across tumor types and does not support further evaluation of this doublet.)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
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
University Health Network, Toronto

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.

Condition or disease Intervention/treatment Phase
Non Small Cell Lung Cancer Renal Cell Carcinoma Biological: Durvalumab Biological: Oleclumab Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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


Arm Intervention/treatment
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
Biological: Durvalumab
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

Biological: Oleclumab
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.




Primary Outcome Measures :
  1. 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)

  2. Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: 3 years ]
  3. Disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: 3 years ]
  4. Duration of response (DoR) [ Time Frame: 3 years ]

Secondary Outcome Measures :
  1. 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

  2. Overall survival (OS) or progression-free survival (PFS) [ Time Frame: 3 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age ≥ 18 years at the time of screening or age of consent according to law
  2. Life expectancy of at least 12 weeks
  3. Written informed consent and any locally required authorization obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
  4. ECOG 0 or 1
  5. Weight ≥35kg
  6. Subjects diagnosed with histologically or cytologically confirmed non small cell lung (NSCLC) or renal cell carcinoma (RCC)
  7. Subjects must have at least 1 measurable lesion according to RECIST version 1.1.
  8. 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
  9. Adequate organ and marrow function
  10. 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
  11. Nonsterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom with spermicide from screening to 90 days after receipt of the final dose of study treatment

Exclusion Criteria:

  1. 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
  2. Prior receipt of any agents targeting CD73, including patients treated with adenosine receptor antagonists, CD39 or CD73 inhibitors
  3. Prior receipt of any innate immune agonists
  4. Patients with NSCLC with known activating EGFR mutations or ALK translocations
  5. Concurrent enrollment in another therapeutic clinical study. Enrollment in observational studies will be allowed
  6. Any toxicity (excluding alopecia) from prior standard therapy that has not been completely resolved to baseline at the time of consent
  7. 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
  8. 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
  9. Active or prior documented autoimmune disorders within the past 3 years prior to the scheduled first dose of study treatment
  10. HIV, Hep A, B, or C
  11. History of primary immunodeficiency, solid organ transplantation, or active tuberculosis
  12. Known allergy or hypersensitivity to investigational product formulations
  13. History of more than one event of infusion related reactions (IRR) requiring permanent discontinuation of IV drug treatment
  14. Active grade 3 or greater edema
  15. History of Grade 3 or greater thromboembolic events in the prior 12 months or thromboembolic event of any grade with ongoing symptoms
  16. Uncontrolled intercurrent
  17. Any history of untreated leptomeningeal disease or cord compression
  18. Untreated CNS metastatic disease
  19. Current or prior use of immunosuppressive medication within 14 days prior to the scheduled first dose of study treatment
  20. Receipt of live, attenuated vaccine within 30 days prior to the scheduled first dose of study treatment
  21. Major surgery within 28 days prior to scheduled first dose of study treatment or still recovering from prior surgery
  22. Females who are pregnant, lactating, or intend to become pregnant during their participation in the study
  23. Subjects who are involuntarily incarcerated or are unable to willingly provide consent or are unable to comply with the protocol procedures
  24. Any condition that would interfere with the evaluation of the study regimen or interpretation of patient safety or study results
  25. Any condition that would interfere with safe administration or evaluation of the investigational products or interpretation of subject safety or study results

Information from the National Library of Medicine

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


Locations
Layout table for location information
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
AstraZeneca
Investigators
Layout table for investigator information
Principal Investigator: Albiruni Razak, MD Princess Margaret Cancer Centre
Layout table for additonal information
Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04262375    
Other Study ID Numbers: DOMINATION
19-6281 ( Other Identifier: University Health Network )
First Posted: February 10, 2020    Key Record Dates
Last Update Posted: November 17, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Renal Cell
Neoplasms by Site
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Durvalumab
Antineoplastic Agents, Immunological
Antineoplastic Agents