A study of AZD4635 with durvalumab and with cabazitaxel and durvalumab in patients with mCRPC. - AARDVARC

Inclusion Criteria

• 1 Histologically confirmed adenocarcinoma of the prostate.
• 2 Known castrate-resistant disease.
• 3 Evidence of disease progression ≤6 months.
• 4 Body weight >30 kg at screening.
• 5 Willingness to adhere to the study treatment-specific contraception requirements.
• 6 Adequate bone marrow reserve and organ function.
• 7 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
• 8 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
• 9 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
• 10 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.