Phase 1/1b Study to Evaluate the Safety and Tolerability of Ciforadenant Alone and in Combination With Atezolizumab in Advanced Cancers

August 27, 2021 updated by: Corvus Pharmaceuticals, Inc.

A Phase 1/1b, Open-Label, Multicenter, Repeat-Dose, Dose-Selection Study of Ciforadenant as Single Agent and in Combination With Atezolizumab in Patients With Selected Incurable Cancers

This is a phase 1/1b open-label, multicenter, dose-selection study of ciforadenant, an oral small molecule targeting the adenosine-A2A receptor on T-lymphocytes and other cells of the immune system. This trial will study the safety, tolerability, and anti-tumor activity of ciforadenant as a single agent and in combination with atezolizumab, a PD-L1 inhibitor against various solid tumors. Ciforadenant blocks adenosine from binding to the A2A receptor. Adenosine suppresses the anti-tumor activity of T cells and other immune cells.

Study Overview

Detailed Description

This is a phase 1/1b open-label, multicenter, dose-selection study of ciforadenant, an oral small molecule targeting the adenosine-A2A receptor on T-lymphocytes and other cells of the immune system. This trial will study the safety, tolerability, and anti-tumor activity of ciforadenant as a single agent and in combination with atezolizumab, an intravenous PD-L1 inhibitor. Ciforadenant blocks adenosine from binding to the A2A receptor. Adenosine suppresses the anti-tumor activity of T cells and other immune cells.

Study Type

Interventional

Enrollment (Actual)

502

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Queensland
      • Brisbane, Queensland, Australia, 4029
        • Royal Brisbane and Women's Hospital
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Monash Health
    • Alberta
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Cross Cancer Institute
    • British Columbia
      • Vancouver, British Columbia, Canada, V5Z 4E6
        • British Columbia Cancer Agency - Vancouver Centre
    • Ontario
      • Ottawa, Ontario, Canada, K1H 8L6
        • The Ottawa Hospital Cancer Centre
    • Arizona
      • Tucson, Arizona, United States, 85719
        • University of Arizona Cancer Center
    • California
      • San Francisco, California, United States, 94143
        • University of California - San Francisco
      • Stanford, California, United States, 94305
        • Stanford Cancer Institute
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami Hospital And Clinics
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush University Medical Center
      • Chicago, Illinois, United States, 60637
        • University of Chicago Medical Center
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Sidney Kimmel Comprehensive Cancer Center - Johns Hopkins University School of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University Of Pittsburgh Medical Center Cancer Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College Of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Renal Cell Carcinoma Inclusion Criteria

  1. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
  2. Documented pathologic diagnosis of clear cell RCC.
  3. Relapsed or refractory to 1-2 prior lines of therapy containing at least an anti-PD-(L)1 agent.
  4. Measurable disease according to RECIST v1.1
  5. Mandatory newly collected tumor biopsy sample obtained prior to treatment initiation.

Renal Cell Carcinoma Exclusion Criteria

  1. History of severe hypersensitivity reaction to monoclonal antibodies.
  2. Has immunodeficiency or requires treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment.
  3. Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease.

Metastatic Castration-Resistant Prostate Cancer Inclusion Criteria

  1. Documentation of disease: progressive CRPC with histologically or cytologically confirmed adenocarcinoma of the prostate.
  2. Patients must have radiologically evident metastatic disease, but it can be measurable or non-measurable disease:

    • Measurable disease: nodal, visceral, or extra nodal lesions according to RECIST v1.1 using a diagnostic computed tomography
    • Non-measurable disease: bone only disease (up to 1/3 of study population) per PCWG3 criteria
  3. 1-3 prior lines of therapy, including at least one newer generation androgen synthesis inhibitor (e.g., abiraterone) or androgen receptor antagonist (e.g., enzalutamide, apalutamide, darolutamide).
  4. Mandatory newly collected tumor biopsy sample obtained prior to treatment initiation.
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

Metastatic Castration-Resistant Prostate Cancer Exclusion Criteria

  1. Has pure small-cell histology and variants with predominant (≥ 50%) neuroendocrine differentiation.
  2. Has a history of severe hypersensitivity reaction to monoclonal antibodies.
  3. Has immunodeficiency or requires treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressant medication during study treatment.
  4. Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1 - Closed
Ciforadenant
100 mg orally twice daily for the first 14 days of each 28-day cycle.
100 mg orally twice daily for 28 days of each 28-day cycle.
200 mg orally once daily for the first 14 days of each 28-day cycle.
Start with 150mg orally twice daily for 28-day cycles; then, increase increments by 100mg/day for 6 dose levels.
Experimental: Cohort 2 - Closed
Ciforadenant
100 mg orally twice daily for the first 14 days of each 28-day cycle.
100 mg orally twice daily for 28 days of each 28-day cycle.
200 mg orally once daily for the first 14 days of each 28-day cycle.
Start with 150mg orally twice daily for 28-day cycles; then, increase increments by 100mg/day for 6 dose levels.
Experimental: Cohort 3 - Closed
Ciforadenant
100 mg orally twice daily for the first 14 days of each 28-day cycle.
100 mg orally twice daily for 28 days of each 28-day cycle.
200 mg orally once daily for the first 14 days of each 28-day cycle.
Start with 150mg orally twice daily for 28-day cycles; then, increase increments by 100mg/day for 6 dose levels.
Experimental: Cohort 4
Ciforadenant + atezolizumab
Ciforadenant 100 mg orally twice daily in combination with atezolizumab intravenously.
Experimental: Cohort 5 - Closed
Ciforadenant
100 mg orally twice daily for the first 14 days of each 28-day cycle.
100 mg orally twice daily for 28 days of each 28-day cycle.
200 mg orally once daily for the first 14 days of each 28-day cycle.
Start with 150mg orally twice daily for 28-day cycles; then, increase increments by 100mg/day for 6 dose levels.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of dose-limiting toxicities (DLTs) of ciforadenant as a single agent and in combination with atezolizumab
Time Frame: 28 days following first administration of ciforadenant
28 days following first administration of ciforadenant
Objective response rate per RECIST v1.1 criteria of ciforadenant as a single agent and in combination with atezolizumab
Time Frame: From start of treatment to end of treatment, up to 72 months
From start of treatment to end of treatment, up to 72 months
Incidence of treatment-emergent adverse events, as assessed by NCI CTCAE v.4.03, of ciforadenant as a single agent and in combination with atezolizumab
Time Frame: Continuously, up to 72 months
Continuously, up to 72 months
Mean and median Area under the curve (AUC) of ciforadenant
Time Frame: Up to 12 months
Up to 12 months
Mean and median Maximum concentration (Cmax) of ciforadenant
Time Frame: Up to 12 months
Up to 12 months
Identify the MDL (maximum dose level) of single agent ciforadenant
Time Frame: From start of treatment to end of treatment, up to 72 months.
From start of treatment to end of treatment, up to 72 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Study Director: Mehrdad Mobasher, MD, MPH, Corvus Pharmaceuticals

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2016

Primary Completion (Actual)

June 1, 2021

Study Completion (Actual)

July 1, 2021

Study Registration Dates

First Submitted

January 8, 2016

First Submitted That Met QC Criteria

January 13, 2016

First Posted (Estimate)

January 14, 2016

Study Record Updates

Last Update Posted (Actual)

August 30, 2021

Last Update Submitted That Met QC Criteria

August 27, 2021

Last Verified

July 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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