Safety, Tolerability, Pharmacokinetics, and Efficacy of Acapatamab in Subjects With mCRPC

NCT ID: NCT03792841

Last Updated: 2025-10-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 212 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-05
• Study Completion Date: 2023-06-29

Brief Summary

A phase 1 study evaluating the safety, tolerability, pharmacokinetics, and efficacy of prostate specific membrane antigen half-life extended bispecific T-cell engager acapatamab in subjects with metastatic castration-resistant prostate cancer, and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Detailed Description

This is a phase I, first-in-human study to evaluate the safety and tolerability of acapatamab; a half-life extended (HLE) bispecific T-cell engager (BiTE®) construct, alone and in combination with pembrolizumab, etanercept prophylaxis and cytochrome P450 (CYP) phenotyping cocktail in subjects with metastatic castration-resistant prostate cancer.

Conditions

Metastatic Castration-resistant Prostate Cancer; Prostate Cancer

Study Design

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

Study Groups

Part 1 Dose-exploration: acapatamab treatment

Part 1 dose-exploration: acapatamab is administered intravenously. The dose-exploration phase of the study will estimate the MTD of acapatamab. RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an MTD.

Group Type: EXPERIMENTAL

acapatamab

Intervention Type: DRUG

Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Part 1 Dose-expansion: acapatamab treatment

Part 1 dose-expansion: acapatamab is administered intravenously at the MTD/RP2D.

Group Type: EXPERIMENTAL

acapatamab

Intervention Type: DRUG

Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Part 2: acapatamab + Pembrolizumab

Part 2: acapatamab is administered intravenously at the MTD/RP2D. Pembrolizumab will be administered intravenously.

Group Type: EXPERIMENTAL

acapatamab

Intervention Type: DRUG

Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Pembrolizumab

Intervention Type: DRUG

Combined with acapatamab for investigational treatment of mCRPC

Part 3: acapatamab + Etanercept Prophylaxis

Part 3: acapatamab is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.

Group Type: EXPERIMENTAL

acapatamab

Intervention Type: DRUG

Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Etanercept

Intervention Type: DRUG

Prophylaxis for acapatamab-related cytokine release syndrome.

Part 4: acapatamab 24 Hour Monitoring

Part 4: acapatamab is administered intravenously at RP2D/MTD with 24-hour monitoring.

Group Type: EXPERIMENTAL

acapatamab

Intervention Type: DRUG

Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Part 5: acapatamab Outpatient Cohort

Part 5: acapatamab is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.

Group Type: EXPERIMENTAL

acapatamab

Intervention Type: DRUG

Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction

Part 6: acapatamab is administered intravenously at RP2D/MTD. A CYP phenotyping cocktail will be administered orally.

Group Type: EXPERIMENTAL

acapatamab

Intervention Type: DRUG

Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Cytochrome P450 (CYP) Cocktail

Intervention Type: DRUG

Evaluate the effect of co-administration of multiple dosing of acapatamab on plasma

Interventions

acapatamab

Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer

Intervention Type: DRUG

Pembrolizumab

Combined with acapatamab for investigational treatment of mCRPC

Intervention Type: DRUG

Etanercept

Prophylaxis for acapatamab-related cytokine release syndrome.

Intervention Type: DRUG

Cytochrome P450 (CYP) Cocktail

Evaluate the effect of co-administration of multiple dosing of acapatamab on plasma

Intervention Type: DRUG

Other Intervention Names

PSMA Targeted Therapy; PD-1 inhibitor; TNF-alpha inhibitor; Cooperstown 5+1 CYP phenotyping cocktail

Eligibility Criteria

Inclusion Criteria

• Subject has provided informed consent prior to initiation of any study specific activities/procedures
• Subjects with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting
• Subjects must have undergone bilateral orchiectomy or must be on continuous ADT with a gonadotropin releasing hormone (GnRH) agonist or antagonist
• Total serum testosterone </= 50 ng/dL or 1.7 nmol/L
• 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
• appearance of 2 or more new lesions in bone scan
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• Life expectancy >/= 6months

Exclusion Criteria

• Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone agonist (LHRH)/GnRH analogue (agonist/antagonist). Subjects on a stable bisophosphonate or denosumab regimen for >/= 30 days prior to randomization are eligible
• Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed with Amgen medical monitor prior to enrollment)
• Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
• Active autoimmune disease or any other diseases requiring immunosuppressive therapy while on study
• Needing chronic systemic corticosteroid therapy (prednisone > 10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-tumor necrosis factor alpha [TNF alpha] therapies) unless stopped 7 days prior to start of first dose
• Myocardial infarction, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of acapatamab

Part 2 only:

• 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 dosing
• History or evidence of interstitial lung disease or active, non-infectious pneumonitis

Part 3 only:

• Evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product

Part 6 only:

Subjects are excluded from this cohort if any of the following additional criteria apply:

• Subjects taking strong OAT3 inhibitors (eg, probenecid) or adjust the dosing to 1 mg PO QD.
• Subjects with latent or active tuberculosis at screening

• Minimum Eligible Age: 18 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

El Camino Hospital

Campbell, California, United States

City of Hope National Medical Center

Duarte, California, United States

City of Hope at Long Beach Elm

Long Beach, California, United States

University of California Los Angeles

Los Angeles, California, United States

Emory University

Atlanta, Georgia, United States

Indiana University

Indianapolis, Indiana, United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Tulane Medical Center

New Orleans, Louisiana, United States

Washington University

St Louis, Missouri, United States

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Weill Cornell Medical College

New York, New York, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Chris OBrien Lifehouse

Camperdown, New South Wales, Australia

Scientia Clinical Research Ltd

Randwick, New South Wales, Australia

Peter MacCallum Cancer Centre

Parkville, Victoria, Australia

Ordensklinikum Linz Elisabethinen

Linz, , Austria

Landeskrankenhaus Salzburg

Salzburg, , Austria

Krankenhaus der Barmherzigen Brueder Wien

Vienna, , Austria

Universitaetsklinikum Allgemeines Krankenhaus Wien

Vienna, , Austria

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

BC Cancer Vancouver

Vancouver, British Columbia, Canada

Institut Gustave Roussy

Villejuif, , France

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Yokohama City University Medical Center

Yokohama, Kanagawa, Japan

Erasmus Medisch Centrum

Rotterdam, , Netherlands

National University Hospital

Singapore, , Singapore

National Cancer Centre Singapore

Singapore, , Singapore

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, , Taiwan

Countries

United States; Australia; Austria; Belgium; Canada; France; Japan; Netherlands; Singapore; Taiwan

References

Dorff T, Horvath LG, Autio K, Bernard-Tessier A, Rettig MB, Machiels JP, Bilen MA, Lolkema MP, Adra N, Rottey S, Greil R, Matsubara N, Tan DSW, Wong A, Uemura H, Lemech C, Meran J, Yu Y, Minocha M, McComb M, Penny HL, Gupta V, Hu X, Jurida G, Kouros-Mehr H, Janat-Amsbury MM, Eggert T, Tran B. A Phase I Study of Acapatamab, a Half-life Extended, PSMA-Targeting Bispecific T-cell Engager for Metastatic Castration-Resistant Prostate Cancer. Clin Cancer Res. 2024 Apr 15;30(8):1488-1500. doi: 10.1158/1078-0432.CCR-23-2978.

Reference Type: BACKGROUND

PMID: 38300720 (View on PubMed)

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20180101

Identifier Type: -

Identifier Source: org_study_id