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

NCT02655822 | Completed Phase 1 DMC

• 1 other identifier: CPI-444-001
• Study Type: interventional
• Target: 502
• Locations: 3 countries
• Sites: 20

Brief Summary

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.

Conditions

Renal Cell Cancer; Metastatic Castration Resistant Prostate Cancer

Keywords

RCC; Kidney Cancer; mCRPC; Prostate Cancer

Outcome Measures

Primary Outcomes (6)

• Incidence of dose-limiting toxicities (DLTs) of ciforadenant as a single agent and in combination with atezolizumab

  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

  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

  Continuously, up to 72 months

• Mean and median Area under the curve (AUC) of ciforadenant

  Up to 12 months

• Mean and median Maximum concentration (Cmax) of ciforadenant

  Up to 12 months

• Identify the MDL (maximum dose level) of single agent ciforadenant

  From start of treatment to end of treatment, up to 72 months.

Study Arms (5)

Cohort 1 - Closed

EXPERIMENTAL

Ciforadenant

Drug: Ciforadenant

Cohort 2 - Closed

EXPERIMENTAL

Ciforadenant

Drug: Ciforadenant

Cohort 3 - Closed

EXPERIMENTAL

Ciforadenant

Drug: Ciforadenant

Cohort 4

EXPERIMENTAL

Ciforadenant + atezolizumab

Drug: Ciforadenant + atezolizumab

Cohort 5 - Closed

EXPERIMENTAL

Ciforadenant

Drug: Ciforadenant

Interventions

Ciforadenant DRUG

100 mg orally twice daily for the first 14 days of each 28-day cycle.

Cohort 1 - Closed

Ciforadenant + atezolizumab DRUG

Ciforadenant 100 mg orally twice daily in combination with atezolizumab intravenously.

Cohort 4

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

• History of severe hypersensitivity reaction to monoclonal antibodies.
• 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.
• Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease.
• Documentation of disease: progressive CRPC with histologically or cytologically confirmed adenocarcinoma of the prostate.
• 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
• 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).
• Mandatory newly collected tumor biopsy sample obtained prior to treatment initiation.
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
• Has pure small-cell histology and variants with predominant (≥ 50%) neuroendocrine differentiation.
• Has a history of severe hypersensitivity reaction to monoclonal antibodies.
• 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.
• Has an active autoimmune disease requiring systemic treatment with in the past 2 years OR a documented history of clinically severe autoimmune disease.

Sponsors & Collaborators

• Corvus Pharmaceuticals, Inc.: lead
• Genentech, Inc.: collaborator

Study Sites (20)

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

University of California - San Francisco

San Francisco, California, 94143, United States

Location

Stanford Cancer Institute

Stanford, California, 94305, United States

Location

Yale University

New Haven, Connecticut, 06510, United States

Location

University of Miami Hospital and Clinics

Miami, Florida, 33136, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Sidney Kimmel Comprehensive Cancer Center - Johns Hopkins University School of Medicine

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Pittsburgh Medical Center Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal Brisbane and Women's Hospital

Brisbane, Queensland, 4029, Australia

Location

Monash Health

Clayton, Victoria, 3168, Australia

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell; Kidney Neoplasms; Prostatic Neoplasms

Interventions

ciforadenant; atezolizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genital Neoplasms, Male; Genital Diseases, Male; Genital Diseases; Prostatic Diseases

Study Officials

• Mehrdad Mobasher, MD, MPH

  Corvus Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 14, 2016
• Study Start: January 1, 2016
• Primary Completion: June 1, 2021
• Study Completion: July 1, 2021
• Last Updated: August 30, 2021

Record last verified: 2021-07

Locations

AU (2); CA (3); US (15)