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).

Study Overview

• Status: Terminated
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Acapatamab; Drug: Enzalutamide; Drug: Abiraterone; Drug: AMG 404

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).

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincents Hospital Sydney
• Denmark
  • Kobenhavn O, Denmark, 2100
    • Rigshospitalet
• Spain
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universidad de Navarra
• Sweden
  • Lund, Sweden, 221 85
    • Skånes Universitetssjukhus
  • Stockholm, Sweden, 171 76
    • Karolinska Universitetssjukhuset Solna
  • Uppsala, Sweden, 75185
    • Akademiska sjukhuset
• United Kingdom
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Orange, California, United States, 92868
      • University of California at Irvine Medical Center
    • San Francisco, California, United States, 94158
      • University of California San Francisco Mission Bay Campus
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Norton Cancer Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Duration of response	Up to 3 years
Overall survival (OS)	Up to 3 years
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
Progression-free survival	Up to 3 years
Time to progression	Up to 3 years
Time to subsequent therapy	Up to 3 years
Maximum plasma concentration (Cmax)	Up to 3 years
Minimum plasma concentration (Cmin)	Up to 3 years
Area under the concentration-time curve (AUC)	Up to 3 years
Accumulation ratio based on area under the concentration-time curve (AUC)	Up to 3 years
Half-life (t1/2)	Up to 3 years
Change from baseline in prostate-specific membrane antigen (PSMA)-positive tumor burden assessed using gallium (GA) 68-labelled PSMA-11 positron emission tomography/computed tomography (PET/CT)	Baseline up to 3 years
Change from baseline in prostate-specific membrane antigen (PSMA)-negative disease burden assessed using 18F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT)	Baseline to 3 years
Time to symptomatic skeletal events	Up to 3 years
Concentration of alkaline phosphatase	Up to 3 years
Concentration of lactate dehydrogenase (LDH)	Up to 3 years
Concentration of hemoglobin	Up to 3 years
Neutrophil-to-lymphocyte ratio	Up to 3 years
Concentration of N-telopeptide in the urine	Up to 3 years

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2021
• Primary Completion (Actual): October 23, 2023
• Study Completion (Actual): October 23, 2023

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: November 13, 2020
• First Posted (Actual): November 17, 2020

Study Record Updates

• Last Update Posted (Actual): November 7, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: mCRPC; Acapatamab; HALF-LIFE EXTENDED (HLE) BITE; 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
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Immunological; Hormone Antagonists; Androgen Antagonists; Immune Checkpoint Inhibitors; Androgens; Androgen Receptor Antagonists
• Other Study ID Numbers: 20190505; 2020-001305-23 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No