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

Recruitment & Eligibility

Status: Recruiting

Sex: Male

Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria: - Parts 1, 2, and 5: 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. 1. Dose exploration phase: Novel antiandrogen therapy must have been given for treatment of metastatic disease. 2. 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 are refractory to a NHT (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 (no prior taxanes). 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 and 4B: 1. Participants with histologically or cytologically confirmed mCRPC who are refractory to 0-2 prior NHT (given in any disease setting depending on the part), and no or 1 taxane (given for hormone sensitive prostate cancer). 2. Dose-expansion phase: at least 1 prior NHT must have been given; 0-1 prior PARP inhibitors are acceptable. 3. 4A: 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. 4. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible). - 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: 1. PSA level >= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart. 2. nodal or visceral progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with PCGW3 modifications. 3. appearance of 2 or more new lesions in bone scan. - Eastern Cooperative Oncology Group performance status of 0-1. - Adequate organ function, defined as follows: 1. Hematological function: 1. absolute neutrophil count >= 1 x 10^9/L (without growth factor support within 7 days from screening assessment). 2. platelet count >= 75 x 10^9/L (without platelet transfusion within 7 days from screening assessment). 3. hemoglobin >= 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment). 2. Renal function: 1. estimated glomerular filtration rate based on Modification of Diet in Renal Disease calculation >= 30 ml/min/1.73 m^2. 3. Hepatic function: 1. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) (or < 5 x ULN for participants with liver involvement). 2. total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for participants with liver metastases). 4. Cardiac function: 1. 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). 2. Baseline electrocardiogram (ECG) QTcF <= 470 msec (average of triplicate values). Part 3-Retreatment group: - Deriving benefit from initial treatment with AMG 509 as evidenced by one of the following: 1. confirmed PSA50 response. 2. 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. Exclusion Criteria: - Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma. - Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within 2 weeks of first dose). - Untreated central nervous system (CNS) metastases or leptomeningeal disease. Participants with a history of treated CNS metastases are eligible if there is radiographic evidence of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. - Participants with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of investigational product administration. - Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy. - History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis); for arterial thrombosis within 12 months of AMG 509 initiation; for venous thrombosis, 6 months and stable on anti-coagulation. - Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 509 with the exception of isch

Exclusion Criteria

Not provided

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events;Incidence of treatment-related adverse events;Dose limiting toxicities (DLTs);Number of participants with changes in vital signs;Number of participants with changes in the electrocardiogram (ECG) records;Number of participants with changes in the clinical laboratory tests results

Secondary Outcome Measures

Name	Time	Method
Maximum serum concentration (Cmax) for AMG 509;Time to maximum serum concentration (Tmax) for AMG 509;Minimum serum concentration (Cmin) for AMG 509;Area under the concentration-time curve (AUC) over the dosing interval for AMG 509;Accumulation following multiple dosing for AMG 509;Objective response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications;Prostate specific antigen (PSA) response;PSA decline of at least 50% from baseline at 12 weeks;Duration of response (DOR) (radiographic and PSA);Time to progression (radiographic and PSA);Progression-free survival (PFS) (radiographic and PSA);6 month radiographic PFS;1, 2, and 3-year radiographic PFS;1, 2, and 3-year overall survival (OS);Circulating tumor cells response (CTC0);Rate of circulating tumor cells (CTC) conversion;Time to symptomatic skeletal events;Alkaline phosphatase (total, bone);Lactate dehydrogenase (LDH);Hemoglobin;Urine N-telopeptide;Neutrophil-to-lymphocyte ratio

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