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NCT04262375 | Withdrawn Phase 2 DMC

• 2 other identifiers: DOMINATION19-6281
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Non Small Cell Lung Cancer; Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (4)

• 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

• Objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  3 years

• Disease control rate (DCR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  3 years

• Duration of response (DoR)

  3 years

Secondary Outcomes (2)

• Incidence of treatment-emergent adverse events (AEs)

  3 years

• Overall survival (OS) or progression-free survival (PFS)

  3 years

Study Arms (1)

Durvalumab and Oleclumab

EXPERIMENTAL

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; Biological: Oleclumab

Interventions

Durvalumab BIOLOGICAL

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.

Also known as: IMFINZI

Durvalumab and Oleclumab

Oleclumab BIOLOGICAL

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.

Durvalumab and Oleclumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1.1.
• 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
• 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

You may not qualify if:

• 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
• History of primary immunodeficiency, solid organ transplantation, or active tuberculosis
• Known allergy or hypersensitivity to investigational product formulations
• History of more than one event of infusion related reactions (IRR) requiring permanent discontinuation of IV drug treatment
• Active grade 3 or greater edema
• History of Grade 3 or greater thromboembolic events in the prior 12 months or thromboembolic event of any grade with ongoing symptoms

Sponsors & Collaborators

• University Health Network, Toronto: lead
• AstraZeneca: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Carcinoma, Renal Cell

Interventions

durvalumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Albiruni Razak, MD

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2020
• First Posted: February 10, 2020
• Study Start: January 1, 2021
• Primary Completion: January 1, 2024
• Study Completion: January 1, 2024
• Last Updated: November 17, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)