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Metastatic Castration-resistant Prostate CancerPhase 1NCT03792841

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

A Phase 1 study testing acapatamab, Pembrolizumab and Etanercept in people with Metastatic Castration-resistant Prostate Cancer and Prostate Cancer, run by Amgen at 30 sites in 10 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
acapatamab, Pembrolizumab and Etanercept
Could I receive a placebo?
No, everyone receives an active treatment
How many people
212 participants
Where
30 sitesin 10 countries
Study dates
5 Feb 2019to 29 Jun 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 15Show fewer
  • 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

Trial locations and contacts

30 sites in 10 countries.

30 sites in 10 countries

United States13 sites

  • Emory University

    Atlanta, Georgia, 30322

  • El Camino Hospital

    Campbell, California, 95008

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Indiana University

    Indianapolis, Indiana, 46202

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

  • Comprehensive Cancer Centers of Nevada

    Las Vegas, Nevada, 89169

  • City of Hope at Long Beach Elm

    Long Beach, California, 90813

  • University of California Los Angeles

    Los Angeles, California, 90095

  • Tulane Medical Center

    New Orleans, Louisiana, 70112

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Weill Cornell Medical College

    New York, New York, 10065

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

Austria4 sites

  • Ordensklinikum Linz Elisabethinen

    Linz, 4020

  • Landeskrankenhaus Salzburg

    Salzburg, 5020

  • Krankenhaus der Barmherzigen Brueder Wien

    Vienna, 1020

  • Universitaetsklinikum Allgemeines Krankenhaus Wien

    Vienna, 1090

Other trials in Austria

Australia3 sites

  • Chris OBrien Lifehouse

    Camperdown, New South Wales, 2050

  • Peter MacCallum Cancer Centre

    Parkville, Victoria, 3050

  • Scientia Clinical Research Ltd

    Randwick, New South Wales, 2031

Other trials in Australia

Belgium2 sites

  • Universite Catholique de Louvain Cliniques Universitaires Saint Luc

    Brussels, 1200

  • Universitair Ziekenhuis Gent

    Ghent, 9000

Other trials in Belgium

Japan2 sites

  • National Cancer Center Hospital East

    Kashiwa-shi, Chiba, 277-8577

  • Yokohama City University Medical Center

    Yokohama, Kanagawa, 232-0024

Other trials in Japan

Singapore2 sites

  • National University Hospital

    Singapore, 119074

  • National Cancer Centre Singapore

    Singapore, 169610

Other trials in Singapore

Canada1 site

  • BC Cancer Vancouver

    Vancouver, British Columbia, V5Z 4E6

Other trials in Canada

France1 site

  • Institut Gustave Roussy

    Villejuif, 94805

Other trials in France

Netherlands1 site

  • Erasmus Medisch Centrum

    Rotterdam, 3015 GD

Other trials in Netherlands

Taiwan1 site

  • Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

    Taoyuan, 33305

Other trials in Taiwan

About this study

Official title: 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

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).

Read the 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.

Being tested
acapatamab, Pembrolizumab, Etanercept, Cytochrome P450 (CYP) Cocktail
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
Medical subject headings
Prostatic Neoplasms, Bites and Stings

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • acapatamabDrug

    Also called PSMA Targeted Therapy

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

  • PembrolizumabDrug

    Also called PD-1 inhibitor

    Combined with acapatamab for investigational treatment of mCRPC

  • EtanerceptDrug

    Also called TNF-alpha inhibitor

    Prophylaxis for acapatamab-related cytokine release syndrome.

  • Cytochrome P450 (CYP) CocktailDrug

    Also called Cooperstown 5+1 CYP phenotyping cocktail

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

Study groups in NCT03792841
Study groupRoleWhat they receive
Part 1 Dose-exploration: acapatamab treatmentExperimentalPart 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.
Receives: Drug: acapatamab
Part 1 Dose-expansion: acapatamab treatmentExperimentalPart 1 dose-expansion: acapatamab is administered intravenously at the MTD/RP2D.
Receives: Drug: acapatamab
Part 2: acapatamab + PembrolizumabExperimentalPart 2: acapatamab is administered intravenously at the MTD/RP2D. Pembrolizumab will be administered intravenously.
Receives: Drug: acapatamab; Drug: Pembrolizumab
Part 3: acapatamab + Etanercept ProphylaxisExperimentalPart 3: acapatamab is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.
Receives: Drug: acapatamab; Drug: Etanercept
Part 4: acapatamab 24 Hour MonitoringExperimentalPart 4: acapatamab is administered intravenously at RP2D/MTD with 24-hour monitoring.
Receives: Drug: acapatamab
Part 5: acapatamab Outpatient CohortExperimentalPart 5: acapatamab is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.
Receives: Drug: acapatamab
Part 6: acapatamab + Cytochrome P450 (CYP) Cocktail Drug InteractionExperimentalPart 6: acapatamab is administered intravenously at RP2D/MTD. A CYP phenotyping cocktail will be administered orally.
Receives: Drug: acapatamab; Drug: Cytochrome P450 (CYP) Cocktail

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with dose-limiting toxicity

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

    Measured: Up to 3 years

  2. Number of participants with treatment-emergent adverse events

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

    Measured: Up to 3 years

  3. Number of participants with treatment-related adverse events

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

    Measured: Up to 3 years

  4. Number of participants with clinically significant changes in vital signs

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

    Measured: Up to 3 years

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

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

    Measured: Up to 3 years

  6. Number of participants with clinically significant changes in clinical laboratory tests

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

    Measured: Up to 3 years

Secondary outcomes (23)

  1. Maximum serum concentration (Cmax) of acapatamab

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

    Measured: Up to 3 years

  2. Minimum serum concentration (Cmin) of acapatamab

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

    Measured: Up to 3 years

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

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

    Measured: Up to 3 years

  4. Accumulation ratio of acapatamab

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

    Measured: Up to 3 years

  5. Half-life of acapatamab

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

    Measured: Up to 3 years

  6. Objective response (OR)

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

    Measured: Up to 3 years

  7. Prostate-specific antigen (PSA) response

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

    Measured: Up to 3 years

  8. Duration of response (DOR) (radiographic and PSA)

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

    Measured: Up to 3 years

  9. Percentage of participants experiencing a response based on 68Gallium (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) response evaluations

    Parts 1, 2 and 3 only.

    Measured: Up to 3 years

  10. Percentage of participants experiencing a response based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) response evaluations

    Parts 1, 2 and 3 only.

    Measured: Up to 3 years

  11. Change in time to progression (radiographic and PSA)

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

    Measured: Up to 3 years

  12. Progression-free survival (PFS) (radiographic and PSA)

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

    Measured: Up to 3 years

  13. 1, 2 and 3-year overall survival (OS)

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

    Measured: Up to 3 years

  14. Percentage of participants experiencing circulating tumor cells (CTC) response

    Parts 1, 2, 3, 4, 5, and 6 of the study. CTC response defined as CTC0 (reduction of CTCs > 0 to 0) or CTC conversion (≥ 5 CTCs/7.5 mL blood to ≤ 4 CTCs/7.5 mL blood)

    Measured: Up to 3 years

  15. Other PCWG3-recommended endpoints - time to symptomatic skeletal events

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

    Measured: Up to 3 years

  16. Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] levels

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

    Measured: Up to 3 years

  17. Other PCWG3-recommended endpoints - hemoglobin levels

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

    Measured: Up to 3 years

  18. Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio

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

    Measured: Up to 3 years

  19. Other PCWG3-recommended endpoints - urine N-telopeptide levels

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

    Measured: Up to 3 years

  20. Other PCWG3-recommended endpoints - alkaline phosphatase [total, bone] levels

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

    Measured: Up to 3 years

  21. Maximum serum concentration (Cmax) of acapatamab when administered with CYP enzymes

    Part 6 only.

    Measured: Up to 3 years

  22. Area under the concentration-time curve over a 24-hour period (AUC24) of acapatamab when administered with CYP enzymes

    Part 6 only.

    Measured: Up to 3 years

  23. Half-life of acapatamab when administered with CYP enzymes

    Part 6 only.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2019
  2. Study start5 Feb 2019
  3. Primary completion29 Jun 2023
  4. Study completion29 Jun 2023

Why it stopped: Sponsor Decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
212 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03792841
Sponsor's protocol ID
20180101
Status last verified
Oct 2025
First submitted
2 Jan 2019
Last updated
16 Oct 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Publications

  • 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.

    PubMed 38300720

  • Hushmandi K, Einollahi B, Lee EHC, Sakaizawa R, Glaviano A, Reiter RJ, Saadat SH, Farani MR, Huh YS, Aref AR, Salimimoghadam S, Kumar AP. Bispecific antibodies as powerful immunotherapeutic agents for urological cancers: Recent innovations based on preclinical and clinical evidence. Int J Biol Sci. 2025 Jan 27;21(4):1410-1435. doi: 10.7150/ijbs.96155. eCollection 2025.

    PubMed 39990653

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing acapatamab, Pembrolizumab and Etanercept in people with Metastatic Castration-resistant Prostate Cancer and Prostate Cancer, run by Amgen at 30 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States, Austria, Australia, Belgium, Japan and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with dose-limiting toxicity (time frame: Up to 3 years). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03792841, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.

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