Clinical trial NCT02655822: Phase 1/1b Study to Evaluate the Safety and Tolerability of Ciforadenant Alone and in Combination With Atezolizumab in Advanced Cancers
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Cell Cancer
Metastatic Castration Resistant Prostate Cancer
Keywords: RCC
Kidney Cancer
mCRPC
Prostate Cancer
Lead sponsor: Corvus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Genentech, Inc.
First posted: 2016-01-14
Enrollment: 502
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of dose-limiting toxicities (DLTs) of ciforadenant as a single agent and in combination with atezolizumab
timeFrame: 28 days following first administration of ciforadenant
measure: Objective response rate per RECIST v1.1 criteria of ciforadenant as a single agent and in combination with atezolizumab
timeFrame: From start of treatment to end of treatment, up to 72 months
measure: 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
timeFrame: Continuously, up to 72 months
measure: Mean and median Area under the curve (AUC) of ciforadenant
timeFrame: Up to 12 months
measure: Mean and median Maximum concentration (Cmax) of ciforadenant
timeFrame: Up to 12 months
measure: Identify the MDL (maximum dose level) of single agent ciforadenant
timeFrame: From start of treatment to end of treatment, up to 72 months.
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Miami
country: United States
facility: University of Miami Hospital and Clinics
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center - Johns Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Cancer Center
state: Pennsylvania
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Brisbane
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Clayton
country: Australia
facility: Monash Health
state: Victoria
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Centre
state: British Columbia
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
Study officials:
affiliation: Corvus Pharmaceuticals
name: Mehrdad Mobasher, MD, MPH
role: STUDY_DIRECTOR
References: