The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of multiple anti-cancer agents in participants with metastatic prostate cancer.
Participants with a diagnosis of histologically confirmed adenocarcinoma of the prostate (no small cell, neuroendocrine, sarcomatoid, spindle or signet cell).
Minimum life expectancy of 3 months or more.
Eastern Cooperative Oncology Group (ECOG) performance status of O or 1 at screening, with no deterioration.
PCWG3 (Prostate Cancer Working Group 3) modified RECIST Version 1.1 evaluable disease.
Any evidence of non adenocarcinomatous forms of prostate cancer (including small cell, spindle cell, signet cell, neuroendocrine, sarcomatous).
Known, unresolved urinary tract obstruction.
Participants with a history of central nervous system metastases.
Symptomatic malignant spinal cord compression or findings indicative of impending cord compression.
Sequential
AZD2265 (FPI-2265)
DrugAZD2265 (FPI-2265) will be administered as an intravenous (IV) injection.
Palacaparib (AZD9574)
DrugPalacaparib (AZD9574) will be administered orally.
Docetaxel
DrugDocetaxel will be administered as an IV infusion.
AZD2287 (Imaging agent)
DrugAZD2287 will be administered as an IV injection.
Part A: Number of participants with treatment-emergent adverse events (TEAEs)including serious adverse events (SAEs), treatment-related AEs (TRAEs) and adverse events of special interests (AESIs)
To assess the safety and tolerability of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Part A: Number of participants with dose limiting toxicities (DLTs)
To assess the safety and tolerability, and characterise the DLTs of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Part B: Number of participants with TEAEs
To further assess the safety and tolerability, and determine the recommended Phase 3 dose (RP3D) of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Part B: Prostate Specific Antigen 50 (PSA50) response rate
PSA50 response rate is defined as proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later, and occurring prior to confirmed PSA progression. PSA50 will be assessed to check the anti-tumour activity of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Part A and Part B: PSA50 response rate
PSA50 response rate is defined as proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later, and occurring prior to confirmed PSA progression. PSA50 will be assessed to check the anti-tumour activity of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B).
Part A and Part B: Prostate Specific Antigen 90 (PSA90) response rate
PSA90 response rate is defined as proportion of participants achieving a ≥ 90% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later, and occurring prior to confirmed PSA progression. PSA90 will be assessed to check the anti-tumour activity of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).
Part A and Part B: Time to PSA50 (TTPSA50) response
TTPSA50 response is defined as the time from date of randomisation/first dose of study intervention until the date of first documented PSA50 response (≥ 50% decrease in PSA from baseline), confirmed by a second consecutive PSA assessment at least 3 weeks later. TTPSA50 response will be assessed to check the anti-tumour activity of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Part A and Part B: Time to PSA90 (TTPSA90) response
TTPSA90 response is defined as the time from date of randomisation/first dose of study intervention until the date of first documented PSA90 response (≥ 90% decrease in PSA from baseline, respectively), confirmed by a second consecutive PSA assessment at least 3 weeks later. TTPSA90 response will be assessed to check the anti-tumour activity of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
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