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

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.