A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer

NCT ID: NCT04702737

Last Updated: 2025-09-12

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

41 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-06-10

Study Completion Date

2024-07-22

Brief Summary

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To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Detailed Description

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Conditions

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Neuroendocrine Prostate Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1: Dose Exploration

The maximum tolerated dose (MTD) will be estimated using isotonic regression (Ji et al, 2010). The recommended phase 2 dose (RP2D) may be identified based on emerging safety data prior to reaching an MTD.

Group Type EXPERIMENTAL

Tarlatamab

Intervention Type DRUG

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

Part 2: Dose Expansion

Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.

Group Type EXPERIMENTAL

Tarlatamab

Intervention Type DRUG

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

Interventions

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Tarlatamab

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

Intervention Type DRUG

Other Intervention Names

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AMG 757

Eligibility Criteria

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Inclusion Criteria

* Participant has provided informed consent prior to initiation of any study specific activities/procedures.
* Men aged ≥ 18 years at time of signing the informed consent.
* Metastatic de novo or treatment-emergent neuroendocrine prostate cancer (NEPC) defined by histology, immunohistochemistry, or genomic analyses of baseline tumor tissue (by local assessment) or circulating tumor DNA (ctDNA) (by local assessment) as per protocol
* At least 1 line of prior systemic treatment per protocol.
* Participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of prostate cancer with neuroendocrine differentiation without a history of bilateral orchiectomy are required to remain on luteinizing hormone-releasing hormone (LHRH) analogue therapy during the course of protocol therapy
* Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 per Prostate Cancer Working Group 3 (PCWG3) modifications
* Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
* Participants with treated brain metastases are eligible provided they meet defined criteria
* Adequate organ function as defined in protocol

Exclusion Criteria

* History of other malignancy within the past 2 years, with exceptions:

* Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
* Adequately treated non-muscle invasive urothelial carcinoma
* History or presence of hematological malignancies unless curatively treated with no evidence of disease ≥ 2 years
* Untreated or symptomatic brain metastases and leptomeningeal disease
* Anti-tumor therapy within 28 days of study day 1; concurrent use of hormone deprivation therapy for hormone refractory prostate cancer is permitted; participants on a stable bisphosphonate or denosumab prior to study day 1 are eligible

Exceptions:

* Participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicities have resolved to Grade ≤ 1
* Prior palliative radiotherapy must have been completed at least 7 days before the first dose of tarlatamab
* Participants who received androgen signaling inhibitor are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade ≤ 1

* Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior study day 1
* Active autoimmune disease requiring systemic treatment within the past 2 years
* Known positive test for human immunodeficiency virus (HIV) or hepatitis
* Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 0 or 1 (with the exception of alopecia or toxicities that are stable and well-controlled)
* History of hypophysitis or pituitary dysfunction
* Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
* Participants on prior delta-like ligand 3 (DLL3)-targeted therapy may be eligible if discussed with Amgen Medical Monitor prior to enrollment
* Evidence of severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection unless agreed upon with Medical Monitor and with no acute symptoms of coronavirus disease 2019 (COVID19) disease within 14 days prior to first dose of investigational product (counted from day of positive test for asymptomatic participants).
Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Mayo Clinic Arizona

Phoenix, Arizona, United States

Site Status

University of California at San Francisco Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

Site Status

University of Chicago

Chicago, Illinois, United States

Site Status

Community Health Network MD Anderson Cancer Center - North

Indianapolis, Indiana, United States

Site Status

Washington University

St Louis, Missouri, United States

Site Status

Weill Cornell Medical College

New York, New York, United States

Site Status

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status

The Ohio State University

Columbus, Ohio, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Chris OBrien Lifehouse

Camperdown, New South Wales, Australia

Site Status

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status

Medizinische Universitaet Graz

Graz, , Austria

Site Status

Ordensklinikum Linz Elisabethinen

Linz, , Austria

Site Status

Landeskrankenhaus Salzburg

Salzburg, , Austria

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Gustave Roussy

Villejuif, , France

Site Status

Keio University Hospital

Shinjuku-ku, Tokyo, Japan

Site Status

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Site Status

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, Spain

Site Status

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United States Australia Austria Belgium France Japan Netherlands Spain United Kingdom

References

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Aggarwal R, Rottey S, Bernard-Tessier A, Mellado B, Kosaka T, Stadler WM, Horvath L, Greil R, O'Neil B, Siddiqui BA, Bauernhofer T, Bilen MA, Eskens F, Sandhu S, Shaw C, Ju CH, Decato BE, Yu B, Aparicio A. Safety and Efficacy of Tarlatamab in Patients with Neuroendocrine Prostate Cancer: Results from the Phase 1b DeLLpro-300 Study. Clin Cancer Res. 2025 Sep 15;31(18):3854-3863. doi: 10.1158/1078-0432.CCR-25-1211.

Reference Type DERIVED
PMID: 40689871 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20200040

Identifier Type: -

Identifier Source: org_study_id

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