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.
- Parts 4A and 4B:
1. Participants with histologically or cytologically confirmed mCRPC who have
received no or 1/2 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).
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 ischemia or non-ST segment elevation myocardial infarction controlled with stent
placement and confirmed by a cardiologist more than 6 months prior to first dose of
AMG 509.
- Any anti-cancer therapy or immunotherapy within 4 weeks of start of first dose, not
including luteinizing hormone-releasing hormone (LHRH)/GnRH analogue
(agonist/antagonist). Participants on a stable bisphosphonate or denosumab regimen for
>= 30 days prior to enrollment are eligible.
- Prior PSMA radionuclide therapy within 2 months prior to AMG 509 unless participant
received < 2 cycles (Note: a participant cannot have received PSMA radionuclide
therapy < 35 days prior to enrollment if 1 cycle was given). Parts 3 and 4: prior PSMA
radionuclide therapy is prohibited.