Clinical Trials /

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

NCT04262375

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief 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
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: DOMINATION
  • SECONDARY ID: 19-6281
  • NCT ID: NCT04262375

Conditions

  • Non Small Cell Lung Cancer
  • Renal Cell Carcinoma

Interventions

DrugSynonymsArms
DurvalumabIMFINZIDurvalumab and Oleclumab
OleclumabDurvalumab and Oleclumab

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Durvalumab and OleclumabExperimentalA 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
  • Oleclumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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)

Secondary Outcome Measures

Measure:Incidence of treatment-emergent adverse events (AEs)
Time Frame:3 years
Safety Issue:
Description:To assess the safety and tolerability of durvalumab and oleclumab in specific disease states in NSCLC and RCC
Measure:Overall survival (OS) or progression-free survival (PFS)
Time Frame:3 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:University Health Network, Toronto

Last Updated

August 12, 2020