A Study of AZD4635 With Durvalumab and With Cabazitaxel and Durvalumab in Patients With mCRPC.

Inclusion Criteria

• Histologically confirmed adenocarcinoma of the prostate.
• Known castrate-resistant disease.
• Evidence of disease progression ≤6 months.
• Body weight >30 kg at screening.
• Willingness to adhere to the study treatment-specific contraception requirements.
• Adequate bone marrow reserve and organ function.
• Adequate organ function for Arm A as demonstrated by all of the following laboratory values:
• Alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN) if no demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases.
• Aspartate aminotransferase (AST) ≤2.5 × ULN if no demonstrable liver metastases or ≤5 × ULN in the presence of liver metastases
• Total bilirubin (TBL) ≤1.5 × ULN
• TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin
• Participants in Arm A must have received the following prior therapy:
• Maximum of 3 lines of therapy in the mCRPC setting
• Prior therapy with one or more NHAs (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide) in either hormone-sensitive or hormone-refractory settings
• Prior therapy with one or more lines of taxanes (eg, docetaxel and/or cabazitaxel)
• Alternatively, must be taxane-ineligible
• Prior therapy can be in either the hormone-sensitive or the hormone-refractory setting
• Adequate organ function for Arm B as demonstrated by all of the following laboratory values:
• AST and/or ALT ≤1.5 × ULN
• TBL ≤ ULN
• TBL ≤2.0 × ULN in the case of known Gilbert syndrome with normal direct bilirubin
• Participants in Arm B must have received the following prior therapy:
• Prior docetaxel (taxane) in either hormone-sensitive or hormone-refractory settings
• Received no prior cytotoxic chemotherapy other than docetaxel for prostate cancer except for estramustine and except adjuvant/neo-adjuvant treatment completed >3 years ago.
• Prior therapy with only one NHAs (eg, abiraterone acetate or enzalutamide; prior apalutamide is not permitted) for treatment of mCRPC in either hormone-sensitive or hormone-refractory settings.
• Be suitable to receive concomitant Granulocyte-colony stimulating factor during all cycles of cabazitaxel.
• Participants who meet inclusion criteria for Arm B will be allocated preferentially to that arm until recruitment to that arm is completed.

Exclusion Criteria

• Active brain metastases or leptomeningeal metastases.
• There must be no requirement for immunosuppressive doses of systemic corticosteroids for at least 2 weeks prior to study enrollment.
• History of pneumonitis requiring corticosteroids, second malignancy that is progressing and/or received active treatment ≤3 years before the first dose of study intervention, and hypersensitivity to polysorbate-80 if allocated to cabazitaxel.
• As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases.
• Creatinine clearance <40 mL/min (calculated by Cockcroft-Gault equation).
• Prior exposure to immune-mediated therapy including.
• Ongoing treatment with warfarin (Coumadin).
• Major surgery (excluding placement of vascular access) within 4 weeks of the first dose of study intervention.