Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer

Inclusion Criteria45

• Parts 1, 2, 5 and 7: Participants with histologically or cytologically confirmed metastatic castration-resistant prostate cancer (mCRPC) who are refractory to a novel antiandrogen therapy (abiraterone acetate and/or enzalutamide, apalutamide, or darolutamide) and have failed at least 1 (but not more than 2) taxane regimens including for metastatic hormone-sensitive prostate cancer (mHSPC) (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Note: A taxane regimen is defined as a minimum exposure of 2 cycles of a taxane. Any NHT that has been administered and has been stopped for reasons other than progression will not be counted as an additional line of treatment.
• Dose exploration phase: Novel antiandrogen therapy must have been given for treatment of metastatic disease.
• Dose-expansion phase: participants must not have had more than 2 NHTs and 2 taxane regimens in any setting, and an additional up to 2 other systemic anti-cancer treatments are allowed (eg, anti-PD1, PARP inhibitors, radioligand therapies, sipuleucel-T, experimental agents) Note: Combinations are considered one systemic anti-cancer treatment.
• Part 3: Participants with histologically or cytologically confirmed mCRPC who have received no or 1-2 prior NHTs (abiraterone acetate, enzalutamide, apalutamide, or darolutamide) given in any disease setting and who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen (unless taxane treatment was administered in HSPC setting). 0 1 prior PARP inhibitors or sipuleucel-T treatments are acceptable. Participants who received prior investigational therapy for the treatment of metastatic disease are not eligible.
• Parts 4A, 4B and 7:
• Participants with histologically or cytologically confirmed mCRPC who have received no or 1-2 prior NHTs (given in any disease setting depending on the part), and no or 1 taxane regimen (for HSPC).
• Dose-expansion phase: at least 1 prior NHT must have been given; 0-1 prior PARP inhibitors are acceptable.
• A: Participants planning to receive abiraterone acetate for the first time (participants who received prior abiraterone acetate are not eligible). Participants may have had exposure to up to 2 NHTs with a similar mechanism of action (apalutamide, enzalutamide or darolutamide) in the non-mCRPC and mCRPC setting.
• Dose-expansion phase: up to approximately 10 participants with prior exposure to abiraterone acetate may be enrolled into Part 4A expansion cohort.
• d. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible).
• Part 6:
• Prior disease progression on 1, and only 1, NHT (either enzalutamide, apalutamide, or darolutamide) is required. NOTE: Prior progression on or intolerance to abiraterone is not allowed.
• No prior treatment with any chemotherapy regimen in the mCRPC setting; ≤ 6 cycles of docetaxel treatment in the mHSPC setting is allowed.
• mCRPC with ≥ 1 RECIST v1.1 measurable lesion that is present on baseline computed tomography (CT) or magnetic resonance imaging (MRI).
• All parts:
• Participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist.
• Total serum testosterone ≤ 50 ng/dL or 1.7 nmol/L.
• Evidence of progressive disease, defined as 1 or more Prostate Cancer Working Group 3 (PCWG3) criteria:
• PSA level ≥ 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart.
• Nodal or visceral progression as defined by RECIST v1.1 with PCGW3 modifications.
• Appearance of 2 or more new lesions in bone scan.
• Eastern Cooperative Oncology Group performance status of 0-1.
• Life expectancy ≥ 3 months.
• Adequate organ function, defined as follows:
• Hematological function:
• absolute neutrophil count ≥ 1 x 10\^9/L (without growth factor support within 7 days from screening assessment).
• platelet count ≥ 75 x 10\^9/L (without platelet transfusion within 7 days from screening assessment).
• hemoglobin ≥ 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment).
• Renal function:
• \. estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation ≥ 30 ml/min/1.73 m\^2.
• Hepatic function:
• aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN) (or \< 5 x ULN for participants with liver involvement).
• total bilirubin (TBL) \< 1.5 x ULN (or \< 2 x ULN for participants with liver metastases).
• Cardiac function:
• left ventricular ejection fraction \> 50% (2-D transthoracic echocardiogram \[ECHO\] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available).
• Baseline electrocardiogram (ECG) QTcF ≤ 470 msec (average of triplicate values).
• Pulmonary function:
• baseline oxygen saturation \> 92% on room air at rest and no oxygen supplementation.
• Part 3-Retreatment group:
• Deriving benefit from initial treatment with AMG 509 as evidenced by one of the following:
• confirmed PSA50 response.
• radiographic stable disease/partial response/complete response during 6 cycles of initial treatment with AMG 509 and without progression during the first 6 cycles.
• No discontinuation for toxicity during the initial treatment with 6 cycles of AMG 509.
• Progressive disease as defined in I106 within 12 months of final dose in their initial treatment with 6 cycles (EOT\_1).
• Willingness to have a fresh tumor biopsy prior to initiating the additional course of treatment, depending on safety and feasibility as assessed by investigator.