Adenosine Receptor Antagonist Combination Therapy for Metastatic Castrate Resistant Prostate Cancer

This is a Phase 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of etrumadenant (AB928)-based combination therapy in participants with metastatic castrate resistant prostate cancer (mCRPC).


Eligibility Criteria:
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 nanomoles per liter \[nmol/L\] or 50 nanograms per deciliter \[ng/dL\])
* Measurable or non-measurable disease as per radiographic evaluation
* Participants with measurable disease may require a fresh tumor biopsy at study entry
* Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
* Life expectancy of at least 3 months
* Adequate hematologic and end-organ function
* Human immunodeficiency virus (HIV), Hepatitis B, and C test results negative prior to first study treatment

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
* Corrected QT interval (QTc) ≥480 msec using Fredericia's QT correction formula (based on an average of triplicate recordings)
* Prior allogeneic 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 medications

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 docetaxel, cabazitaxel, topoisomerase 1 inhibitors, 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