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

NCT03792841 | Terminated Phase 1 FDA Drug

• 1 other identifier: 20180101
• Study Type: interventional
• Target: 212
• Locations: 9 countries
• Sites: 26

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).

Conditions

Metastatic Castration-resistant Prostate Cancer; Prostate Cancer

Keywords

acapatamab; HLE-BiTE®; mCRPC; Metastatic Castration-resistant Prostate Cancer; Prostate cancer; PSMA; BiTE®; Bispecific T-Cell engager; Immunotherapy; Immuno-oncology; Immunooncology; Solid tumor; PSMA Targeted Therapy

Outcome Measures

Primary Outcomes (6)

• Number of participants with dose-limiting toxicity

  Parts 1, 2, 3, 4, 5, and 6 of the study

  Up to 3 years

• Number of participants with treatment-emergent adverse events

  Parts 1, 2, 3, 4, 5, and 6 of the study

  Up to 3 years

• Number of participants with treatment-related adverse events

  Parts 1, 2, 3, 4, 5, and 6 of the study

  Up to 3 years

• Number of participants with clinically significant changes in vital signs

  Parts 1, 2, 3, 4, 5, and 6 of the study

  Up to 3 years

• Number of participants with clinically significant changes in electrocardiogram (ECG)

  Parts 1, 2, 3, 4, 5, and 6 of the study

  Up to 3 years

• Number of participants with clinically significant changes in clinical laboratory tests

  Parts 1, 2, 3, 4, 5, and 6 of the study

  Up to 3 years

Secondary Outcomes (23)

• Maximum serum concentration (Cmax) of acapatamab

  Up to 3 years

• Minimum serum concentration (Cmin) of acapatamab

  Up to 3 years

• Area under the concentration-time curve (AUC) over the dosing interval of acapatamab

  Up to 3 years

• Accumulation ratio of acapatamab

  Up to 3 years

• Half-life of acapatamab

  Up to 3 years

Study Arms (7)

Part 1 Dose-exploration: acapatamab treatment

EXPERIMENTAL

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.

Drug: acapatamab

Part 1 Dose-expansion: acapatamab treatment

EXPERIMENTAL

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

Drug: acapatamab

Part 2: acapatamab + Pembrolizumab

EXPERIMENTAL

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

Drug: acapatamab; Drug: Pembrolizumab

Part 3: acapatamab + Etanercept Prophylaxis

EXPERIMENTAL

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

Drug: acapatamab; Drug: Etanercept

Part 4: acapatamab 24 Hour Monitoring

EXPERIMENTAL

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

Drug: acapatamab

Part 5: acapatamab Outpatient Cohort

EXPERIMENTAL

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

Drug: acapatamab

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

EXPERIMENTAL

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

Drug: acapatamab; Drug: Cytochrome P450 (CYP) Cocktail

Interventions

acapatamab DRUG

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

Also known as: PSMA Targeted Therapy

Part 1 Dose-expansion: acapatamab treatment; Part 1 Dose-exploration: acapatamab treatment; Part 2: acapatamab + Pembrolizumab; Part 3: acapatamab + Etanercept Prophylaxis; Part 4: acapatamab 24 Hour Monitoring; Part 5: acapatamab Outpatient Cohort; Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug Interaction

Pembrolizumab DRUG

Combined with acapatamab for investigational treatment of mCRPC

Also known as: PD-1 inhibitor

Part 2: acapatamab + Pembrolizumab

Etanercept DRUG

Prophylaxis for acapatamab-related cytokine release syndrome.

Also known as: TNF-alpha inhibitor

Part 3: acapatamab + Etanercept Prophylaxis

Cytochrome P450 (CYP) Cocktail DRUG

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

Also known as: Cooperstown 5+1 CYP phenotyping cocktail

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

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (30)

El Camino Hospital

Campbell, California, 95008, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

City of Hope at Long Beach Elm

Long Beach, California, 90813, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

Tulane Medical Center

New Orleans, Louisiana, 70112, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Scientia Clinical Research Ltd

Randwick, New South Wales, 2031, Australia

Location

Peter MacCallum Cancer Centre

Parkville, Victoria, 3050, Australia

Location

Ordensklinikum Linz Elisabethinen

Linz, 4020, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Krankenhaus der Barmherzigen Brueder Wien

Vienna, 1020, Austria

Location

Universitaetsklinikum Allgemeines Krankenhaus Wien

Vienna, 1090, Austria

Location

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

BC Cancer Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Yokohama City University Medical Center

Yokohama, Kanagawa, 232-0024, Japan

Location

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

Location

National University Hospital

Singapore, 119074, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 38300720 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Prostatic Neoplasms; Bites and Stings

Interventions

pembrolizumab; Immune Checkpoint Inhibitors; Etanercept; Cytochrome P-450 Enzyme System

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Cytochromes; Enzymes and Coenzymes; Mixed Function Oxygenases; Oxygenases; Oxidoreductases; Enzymes; Hemeproteins

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 3, 2019
• Study Start: February 5, 2019
• Primary Completion: June 29, 2023
• Study Completion: June 29, 2023
• Last Updated: October 16, 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 (or other new use) 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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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 (3); JP (2); BE (2); CA (1); NL (1); FR (1); US (13); SG (2); TW (1)