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

Non Small Cell Lung Cancer Clinical Trial

— DOMINATION  

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Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04262375
• Other study ID #: DOMINATION
• Secondary ID: 19-6281
• Status: Withdrawn
• Phase: Phase 2
• Start date: January 2021
• Est. completion date: January 2024

Study information

• Verified date: November 2020
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Non Small Cell Lung Cancer
• Renal Cell Carcinoma

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	AstraZeneca

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).	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)	3 years
Primary	Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1		3 years
Primary	Disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1		3 years
Primary	Duration of response (DoR)		3 years
Secondary	Incidence of treatment-emergent adverse events (AEs)	To assess the safety and tolerability of durvalumab and oleclumab in specific disease states in NSCLC and RCC	3 years
Secondary	Overall survival (OS) or progression-free survival (PFS)		3 years