Purpose

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

Condition

Eligibility

Eligible Ages
Between 18 Years and 99 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Acapatamab and Enzalutamide: Dose Exploration
The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with enzalutamide.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: Enzalutamide
    Enzalutamide will be administered orally.
    Other names:
    • Androgen receptor inhibitor
Experimental
Acapatamab and Enzalutamide: Dose Expansion
Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with enzalutamide.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: Enzalutamide
    Enzalutamide will be administered orally.
    Other names:
    • Androgen receptor inhibitor
Experimental
Acapatamab and Abiraterone: Dose Exploration
The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with abiraterone.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: Abiraterone
    Abiraterone will be administered orally.
    Other names:
    • Cytochrome P450 (CYP)17 inhibitor
Experimental
Acapatamab and Abiraterone: Dose Expansion
Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with abiraterone.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: Abiraterone
    Abiraterone will be administered orally.
    Other names:
    • Cytochrome P450 (CYP)17 inhibitor
Experimental
Acapatamab and AMG 404: Dose Exploration
The dose-exploration part of the study will estimate the MTD/RP2D of Acapatamab in combination with AMG 404.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: AMG 404
    AMG 404 will be administered as an intravenous (IV) infusion.
    Other names:
    • PD-1 inhibitor
Experimental
Acapatamab and AMG 404: Dose Expansion
Following dose exploration, dose expansion will be conducted to confirm the safety and tolerability of the selected dose and to further evaluate the efficacy of Acapatamab in combination with AMG 404.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: AMG 404
    AMG 404 will be administered as an intravenous (IV) infusion.
    Other names:
    • PD-1 inhibitor
Active Comparator
AMG 404 Monotherapy
AMG 404 monotherapy is being conducted to evaluate the preliminary anti-tumor activity of PD-1 inhibition in the mCRPC population.
  • Drug: AMG 404
    AMG 404 will be administered as an intravenous (IV) infusion.
    Other names:
    • PD-1 inhibitor
Experimental
Acapatamab and Enzalutamide: Dose Expansion Asia Cohort
Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with enzalutamide for subjects in Asia.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: Enzalutamide
    Enzalutamide will be administered orally.
    Other names:
    • Androgen receptor inhibitor
Experimental
Acapatamab and Abiraterone: Dose Expansion Asia Cohort
Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with abiraterone for subjects in Asia.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: Abiraterone
    Abiraterone will be administered orally.
    Other names:
    • Cytochrome P450 (CYP)17 inhibitor
Experimental
Acapatamab and AMG 404: Dose Expansion Asia Cohort
Following dose exploration, dose expansion will be conducted in the Asia cohort at the combination MTD/RP2D determined in dose exploration to confirm the safety, tolerability and PK of Acapatamab in combination with AMG 404 for subjects in Asia.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy
  • Drug: AMG 404
    AMG 404 will be administered as an intravenous (IV) infusion.
    Other names:
    • PD-1 inhibitor
Experimental
Acapatamab Monotherapy
Acapatamab monotherapy is being conducted to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of Acapatamab in subjects with mCRPC.
  • Drug: Acapatamab
    Acapatamab will be administered as an intravenous (IV) infusion.
    Other names:
    • PSMA targeted therapy

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294

More Details

Status
Recruiting
Sponsor
Amgen

Study Contact

Amgen Call Center
866-572-6436
medinfo@amgen.com

Detailed Description

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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.