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

Renal Cell Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02655822
• Other study ID #: CPI-444-001
• Status: Completed
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: July 2021

Study information

• Verified date: July 2021
• Source: Corvus Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 502
• Est. completion date: July 2021
• Est. primary completion date: June 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Metastatic Castration Resistant Prostate Cancer
• Prostatic Neoplasms
• Renal Cell Cancer

Intervention

Drug:
• Ciforadenant
100 mg orally twice daily for the first 14 days of each 28-day cycle.
• Ciforadenant
100 mg orally twice daily for 28 days of each 28-day cycle.
• Ciforadenant
200 mg orally once daily for the first 14 days of each 28-day cycle.
• Ciforadenant + atezolizumab
Ciforadenant 100 mg orally twice daily in combination with atezolizumab intravenously.
• Ciforadenant
Start with 150mg orally twice daily for 28-day cycles; then, increase increments by 100mg/day for 6 dose levels.

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Brisbane	Queensland
Australia	Monash Health	Clayton	Victoria
Canada	Cross Cancer Institute	Edmonton	Alberta
Canada	The Ottawa Hospital Cancer Centre	Ottawa	Ontario
Canada	British Columbia Cancer Agency - Vancouver Centre	Vancouver	British Columbia
United States	Sidney Kimmel Comprehensive Cancer Center - Johns Hopkins University School of Medicine	Baltimore	Maryland
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	University of Miami Hospital and Clinics	Miami	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Pittsburgh Medical Center Cancer Center	Pittsburgh	Pennsylvania
United States	University of California - San Francisco	San Francisco	California
United States	Stanford Cancer Institute	Stanford	California
United States	University of Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Corvus Pharmaceuticals, Inc.	Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose-limiting toxicities (DLTs) of ciforadenant as a single agent and in combination with atezolizumab		28 days following first administration of ciforadenant
Primary	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
Primary	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
Primary	Mean and median Area under the curve (AUC) of ciforadenant		Up to 12 months
Primary	Mean and median Maximum concentration (Cmax) of ciforadenant		Up to 12 months
Primary	Identify the MDL (maximum dose level) of single agent ciforadenant		From start of treatment to end of treatment, up to 72 months.