for males ages 18-99 (full criteria)
at San Francisco, California and other locations
study started
estimated completion



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

Official Title

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, 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).


Metastatic Castration-resistant Prostate Cancer, Acapatamab, HALF-LIFE EXTENDED (HLE) BITE, mCRPC, 68, Gallium (68Ga)-prostate-specific membrane, antigen (PSMA)-11 positron emission, tomography(PET)/computed tomography (CT), and, 18, F-fluorodeoxyglucose (FDG) PET/CT, based response evaluation, Bispecific T cell Engager, BITE, Prostatic Neoplasms, Immune Checkpoint Inhibitors, Androgens, Androgen Receptor Antagonists, Enzalutamide, Abiraterone, AMG 404, AMG 404 Monotherapy, Acapatamab Monotherapy


For males ages 18-99

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


  • UCSF Mission Bay Campus
    San Francisco California 94158 United States
  • University of California at Irvine Medical Center
    Orange California 92868 United States


in progress, not accepting new patients
Start Date
Completion Date
AmgenTrials clinical trials website
Phase 1/2 research study
Study Type
About 65 people participating
Last Updated