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

NCT04631601 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 201905052020-001305-23
• Study Type: interventional
• Target: 65
• Locations: 6 countries
• Sites: 14

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).

Conditions

Metastatic Castration-resistant Prostate Cancer

Keywords

Acapatamab; HALF-LIFE EXTENDED (HLE) BITE; mCRPC; Metastatic Castration-resistant Prostate Cancer; 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

Outcome Measures

Primary Outcomes (5)

• Dose exploration only: Number of participants who experience dose limiting toxicities (DLTs)

  The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab. The analysis of dose-limiting toxicity (DLT) will be conducted on the DLT Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab with an evaluable DLT endpoint. If a single subject experiences more than 1 DLT it will be counted as 1. The DLT endpoint is evaluable if either: 1\) the subject experiences a DLT; or 2) the subject does not experience a DLT after receiving all planned doses within the 28-day DLT window in cycle 1.

  Up to 3 years

• Number of participants who experience one or more treatment-emergent adverse events (TEAEs)

  Up to 3 years

• Number of participants who experience one or more treatment-related adverse events

  Up to 3 years

• Number of participants who experience a clinically significant change in vital signs

  Up to 3 years

• Number of participants who experience a clinically significant change in clinical laboratory tests

  Up to 3 years

Secondary Outcomes (21)

• Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications

  Up to 3 years

• Number of participants who experience circulating tumor cell (CTC) response

  Up to 3 years

• Number of participants who experience prostate-specific antigen (PSA) response rate

  Up to 3 years

• Duration of response

  Up to 3 years

• Overall survival (OS)

  Up to 3 years

Study Arms (11)

Acapatamab and Enzalutamide: Dose Exploration

EXPERIMENTAL

The dose-exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with enzalutamide.

Drug: Acapatamab; Drug: Enzalutamide

Acapatamab and Enzalutamide: Dose Expansion

EXPERIMENTAL

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; Drug: Enzalutamide

Acapatamab and Abiraterone: Dose Exploration

EXPERIMENTAL

The dose exploration part of the study will estimate the MTD/recommended phase 2 dose (RP2D) of Acapatamab in combination with abiraterone.

Drug: Acapatamab; Drug: Abiraterone

Acapatamab and Abiraterone: Dose Expansion

EXPERIMENTAL

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; Drug: Abiraterone

Acapatamab and AMG 404: Dose Exploration

EXPERIMENTAL

The dose-exploration part of the study will estimate the MTD/RP2D of Acapatamab in combination with AMG 404.

Drug: Acapatamab; Drug: AMG 404

Acapatamab and AMG 404: Dose Expansion

EXPERIMENTAL

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; Drug: AMG 404

AMG 404 Monotherapy

ACTIVE COMPARATOR

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

Drug: AMG 404

Acapatamab and Enzalutamide: Dose Expansion Asia Cohort

EXPERIMENTAL

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; Drug: Enzalutamide

Acapatamab and Abiraterone: Dose Expansion Asia Cohort

EXPERIMENTAL

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; Drug: Abiraterone

Acapatamab and AMG 404: Dose Expansion Asia Cohort

EXPERIMENTAL

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; Drug: AMG 404

Acapatamab Monotherapy

EXPERIMENTAL

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

Drug: Acapatamab

Interventions

Acapatamab DRUG

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

Also known as: PSMA targeted therapy

Acapatamab Monotherapy; Acapatamab and AMG 404: Dose Expansion; Acapatamab and AMG 404: Dose Expansion Asia Cohort; Acapatamab and AMG 404: Dose Exploration; Acapatamab and Abiraterone: Dose Expansion; Acapatamab and Abiraterone: Dose Expansion Asia Cohort; Acapatamab and Abiraterone: Dose Exploration; Acapatamab and Enzalutamide: Dose Expansion; Acapatamab and Enzalutamide: Dose Expansion Asia Cohort; Acapatamab and Enzalutamide: Dose Exploration

Enzalutamide DRUG

Enzalutamide will be administered orally.

Also known as: Androgen receptor inhibitor

Acapatamab and Enzalutamide: Dose Expansion; Acapatamab and Enzalutamide: Dose Expansion Asia Cohort; Acapatamab and Enzalutamide: Dose Exploration

Abiraterone DRUG

Abiraterone will be administered orally.

Also known as: Cytochrome P450 (CYP)17 inhibitor

Acapatamab and Abiraterone: Dose Expansion; Acapatamab and Abiraterone: Dose Expansion Asia Cohort; Acapatamab and Abiraterone: Dose Exploration

AMG 404 DRUG

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

Also known as: PD-1 inhibitor

AMG 404 Monotherapy; Acapatamab and AMG 404: Dose Expansion; Acapatamab and AMG 404: Dose Expansion Asia Cohort; Acapatamab and AMG 404: Dose Exploration

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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))

You may not qualify if:

• 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:
• Subjects planning to receive enzalutamide for the first time for mCRPC
• Use of strong CYP2C8 inhibitors or strong CYP3A4 inducers
• Use of narrow therapeutic index drugs that are substrates of CYP3A4, CYP2C9 or CYP2C19

Sponsors & Collaborators

• Amgen: lead

Study Sites (14)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California at Irvine Medical Center

Orange, California, 92868, United States

Location

University of California San Francisco Mission Bay Campus

San Francisco, California, 94158, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40207, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

St Vincents Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Rigshospitalet

København Ø, 2100, Denmark

Location

Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain

Location

Skanes universitetssjukhus

Lund, 221 85, Sweden

Location

Karolinska Universitetssjukhuset Solna

Stockholm, 171 76, Sweden

Location

Akademiska sjukhuset

Uppsala, 75185, Sweden

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Bites and Stings

Interventions

enzalutamide; Androgen Receptor Antagonists; abiraterone; Cytochrome P-450 Enzyme System; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Androgen Antagonists; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Cytochromes; Enzymes and Coenzymes; Mixed Function Oxygenases; Oxygenases; Oxidoreductases; Enzymes; Hemeproteins; Proteins; Amino Acids, Peptides, and Proteins; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2020
• First Posted: November 17, 2020
• Study Start: January 15, 2021
• Primary Completion: October 23, 2023
• Study Completion: October 23, 2023
• Last Updated: October 7, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

AU (1); SE (3); DK (1); ES (1); GB (1); US (7)