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

Sponsor

Corvus Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02655822

Collaborator

Genentech, Inc. (Industry)

502

Enrollment

Locations

Arms

Duration (Months)

25.1

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Renal Cell Cancer Metastatic Castration Resistant Prostate Cancer	Drug: Ciforadenant Drug: Ciforadenant Drug: Ciforadenant Drug: Ciforadenant + atezolizumab Drug: Ciforadenant	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

502 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Study Start Date :

Jan 1, 2016

Actual Primary Completion Date :

Jun 1, 2021

Actual Study Completion Date :

Jul 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Renal Cell Carcinoma Inclusion Criteria

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.

Renal Cell Carcinoma Exclusion Criteria

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.

Metastatic Castration-Resistant Prostate Cancer Inclusion Criteria

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

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).
Mandatory newly collected tumor biopsy sample obtained prior to treatment initiation.
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

Metastatic Castration-Resistant Prostate Cancer Exclusion Criteria

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center	Tucson	Arizona	United States	85719
2	University of California - San Francisco	San Francisco	California	United States	94143
3	Stanford Cancer Institute	Stanford	California	United States	94305
4	Yale University	New Haven	Connecticut	United States	06510
5	University of Miami Hospital and Clinics	Miami	Florida	United States	33136
6	Rush University Medical Center	Chicago	Illinois	United States	60612
7	University of Chicago Medical Center	Chicago	Illinois	United States	60637
8	Sidney Kimmel Comprehensive Cancer Center - Johns Hopkins University School of Medicine	Baltimore	Maryland	United States	21287
9	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
10	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
11	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
12	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
13	Cleveland Clinic	Cleveland	Ohio	United States	44195
14	University of Pittsburgh Medical Center Cancer Center	Pittsburgh	Pennsylvania	United States	15232
15	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
16	Royal Brisbane and Women's Hospital	Brisbane	Queensland	Australia	4029
17	Monash Health	Clayton	Victoria	Australia	3168
18	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
19	British Columbia Cancer Agency - Vancouver Centre	Vancouver	British Columbia	Canada	V5Z 4E6
20	The Ottawa Hospital Cancer Centre	Ottawa	Ontario	Canada	K1H 8L6