Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer

For males ages 18 years and up

General Inclusion Criteria:

• Male participants; age ≥ 18 years
• Metastatic castrate-resistant prostate cancer while on anti-androgen treatment with castrate levels of testosterone (≤1.7 nmol/L or 50 ng/dL)
• Measurable or non-measurable disease as per radiographic evaluation
• Participants with measurable disease may require a fresh tumor biopsy at study entry
• Performance status of 0 or 1
• Life expectancy of at least 3 months
• Adequate hematologic and end-organ function
• Inclusion Criteria for Participants receiving an enzalutamide-containing treatment
• Disease progression after prior treatment with abiraterone
• Inclusion Criteria for Participants receiving a docetaxel-containing treatment
• Disease progression after prior androgen synthesis inhibitor therapy
• Inclusion Criteria for all other Participants
• Disease progression after prior androgen synthesis inhibitor treatment and up to 2 prior lines of taxane chemotherapy

General Exclusion Criteria:

• Prior treatment with immune checkpoint blockade therapy
• Prior anticancer treatment including approved agents, systemic radiotherapy, or investigational therapy, within 2-4 weeks prior first study treatment
• ECG (Electrocardiogram) result with QTcF ≥480 msec
• Prior stem cell or solid organ transplantation
• Prior treatment with drugs that stimulate the immune system within 4 weeks prior to first study treatment
• Prior treatment with drugs that suppress the immune system within 2 weeks prior to first study treatment
• Received a live, attenuated vaccine within 4 weeks prior to first study treatment, or may need to receive a vaccine during study treatment
• Presence of metastases in the brain or cancer spreading into the cerebrospinal fluid -CSF (leptomeningeal disease)
• Prior pulmonary fibrosis, pneumonia, or pneumonitis
• Cancer other than prostate within 2 years prior to study entry, except for some cancers with a low risk of spreading like non-melanoma skin
• Prior treatment with an agent targeting the adenosine pathway
• No oral or IV antibiotics within 2 weeks prior to first study treatment
• No severe infection within 4 weeks prior to first study treatment
• No clinically significant cardiac disease
• Inability to swallow oral medications
• HIV, Hepatitis B, and C test results negative prior to first study treatment
• Exclusion Criteria for Participants receiving an enzalutamide-containing treatment
• Prior treatment with docetaxel, cabazitaxel, or other taxane chemotherapy (prior docetaxel [up to 6 cycles] for hormone-sensitive prostate cancer is allowed if the last dose was at least 6 months prior to study treatment initiation)
• Prior treatment with enzalutamide or similar therapy other than abiraterone
• Active or history of autoimmune disease or immune deficiency
• History of severe allergic reactions to antibody therapy
• Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment
• Exclusion Criteria for Participants receiving a docetaxel-containing treatment
• Prior treatment with docetaxel, cabazitaxel, or other taxane chemotherapy
• Active or history of autoimmune disease or immune deficiency
• History of severe allergic reactions to antibody therapy
• Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment
• Exclusion Criteria for all other Participants
• Prior treatment with 3 or more lines of taxane chemotherapy
• Active or history of autoimmune disease or immune deficiency
• History of severe allergic reactions to antibody therapy
• Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment