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

NCT ID: NCT04631601

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-15
• Study Completion Date: 2023-10-23

Brief Summary

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

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).

Conditions

Metastatic Castration-resistant Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Enzalutamide

Intervention Type: DRUG

Enzalutamide will be administered orally.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

Enzalutamide

Intervention Type: DRUG

Enzalutamide will be administered orally.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

Abiraterone

Intervention Type: DRUG

Abiraterone will be administered orally.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

Abiraterone

Intervention Type: DRUG

Abiraterone will be administered orally.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

AMG 404

Intervention Type: DRUG

AMG 404 will be administered as an intravenous (IV) infusion.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

AMG 404

Intervention Type: DRUG

AMG 404 will be administered as an intravenous (IV) infusion.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

AMG 404 Monotherapy

AMG 404 monotherapy is being conducted to evaluate the preliminary anti-tumor activity of PD-1 inhibition in the mCRPC population.

Group Type: ACTIVE_COMPARATOR

AMG 404

Intervention Type: DRUG

AMG 404 will be administered as an intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

Enzalutamide

Intervention Type: DRUG

Enzalutamide will be administered orally.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

Abiraterone

Intervention Type: DRUG

Abiraterone will be administered orally.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

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.

Group Type: EXPERIMENTAL

AMG 404

Intervention Type: DRUG

AMG 404 will be administered as an intravenous (IV) infusion.

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

Acapatamab Monotherapy

Acapatamab monotherapy is being conducted to evaluate safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of Acapatamab in subjects with mCRPC.

Group Type: EXPERIMENTAL

Acapatamab

Intervention Type: DRUG

Acapatamab will be administered as an intravenous (IV) infusion.

Interventions

Enzalutamide

Enzalutamide will be administered orally.

Intervention Type: DRUG

Abiraterone

Abiraterone will be administered orally.

Intervention Type: DRUG

AMG 404

AMG 404 will be administered as an intravenous (IV) infusion.

Intervention Type: DRUG

Acapatamab

Acapatamab will be administered as an intravenous (IV) infusion.

Intervention Type: DRUG

Other Intervention Names

PSMA targeted therapy; Androgen receptor inhibitor; Cytochrome P450 (CYP)17 inhibitor; PD-1 inhibitor

Eligibility Criteria

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))

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

• Subjects who are refractory to a novel antiandrogen therapy. Subjects must be ineligible for or refuse taxane therapy.

• 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

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:

• 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:

• 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:

• 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:

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 99 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of California at Irvine Medical Center

Orange, California, United States

University of California San Francisco Mission Bay Campus

San Francisco, California, United States

University of Chicago

Chicago, Illinois, United States

Norton Cancer Institute

Louisville, Kentucky, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

St Vincents Hospital Sydney

Darlinghurst, New South Wales, Australia

Rigshospitalet

København Ø, , Denmark

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Skanes universitetssjukhus

Lund, , Sweden

Karolinska Universitetssjukhuset Solna

Stockholm, , Sweden

Akademiska sjukhuset

Uppsala, , Sweden

Royal Marsden Hospital

Sutton, , United Kingdom

Countries

United States; Australia; Denmark; Spain; Sweden; United Kingdom

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

2020-001305-23

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

20190505

Identifier Type: -

Identifier Source: org_study_id