Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)

A Master Protocol Evaluating the Safety and Efficacy of Therapies for Metastatic Castration-resistant Prostate Cancer (mCRPC)

This is a master protocol designed to evaluate the safety and efficacy of investigational therapies in participants with metastatic castration-resistant prostate cancer (mCRPC).

This is a master protocol designed to evaluate the safety, tolerability, and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and efficacy of Acapatamab, in combination with enzalutamide, abiraterone, or the PD1 inhibitor AMG 404, AMG 404 monotherapy, as well as Acapatamab monotherapy, in participants with metastatic castration-resistant prostate cancer (mCRPC).

All parts

Inclusion Criteria:

• ≥ 18 years of age (or legal adult age within country)
• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate
• Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist (testosterone ≤ 50 ng/dL (or 1.7 nmol/L))

Exclusion Criteria:

• Central nervous system (CNS) metastases or leptomeningeal disease

• History or presence of clinically relevant CNS pathology

• Confirmed history or current autoimmune disease or other diseases requiring permanent immunosuppressive therapy

• Myocardial infarction, uncontrolled hypertension, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months

• Prior treatment with a taxane for mCRPC

• Major surgery and/or Radiation within 4 weeks

• History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with medical monitor and meeting the following criteria:

  • Negative test for SARS-CoV-2 RNA by real time polymerase chain reaction (RT-PCR) within 72 hours of first dose of Acapatamab (or AMG 404 in Part 3)
  • No acute symptoms of COVID-19 disease within 10 days prior to first dose of Acapatamab (or AMG 404 in Part 3) (counted from day of positive test for asymptomatic subjects)

Prior/Concurrent Clinical Study Experience

• Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded with the exception of investigational scans.

Subprotocol A only:

Inclusion criteria

• Subjects planning to receive enzalutamide for the first time for mCRPC

Exclusion criteria

• Use of strong CYP2C8 inhibitors or strong CYP3A4 inducers
• Use of narrow therapeutic index drugs that are substrates of CYP3A4, CYP2C9 or CYP2C19

Subprotocol B only:

Inclusion criteria

• Subjects planning to receive abiraterone for the first time for mCRPC Exclusion criteria
• Baseline moderate and severe hepatic impairment (Child-Pugh Class B and C)
• Presence of uncontrolled hypertension, hypokalemia, or fluid retention
• History or presence of adrenocortical insufficiency
• Use of concomitant medications that are sensitive substrates for CYP2D6 with a narrow therapeutic index
• Use of strong CYP3A4 inducers

Subprotocol C only:

Inclusion criteria

• Subjects who are refractory to a novel antiandrogen therapy. Subjects must be ineligible for or refuse taxane therapy.
• Evidence of progressive disease, defined as 1 or more 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 1.1 with PCGW3 modifications, and/or appearance of 2 or more new lesions in bone scan Exclusion criteria
• History or evidence of interstitial lung disease or active, non-infectious pneumonitis
• Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a grade 3 or higher immune-related adverse event prior to first day of dose

Subprotocol D only:

Inclusion criteria

• Subjects may have had novel hormonal therapies (NHT; eg, abiraterone, enzalutamide, apalutamide, or darolutamide) for prostate cancer, but no more than 1 NHT for metastatic prostate cancer
• Ineligible for or refuse taxane therapy