A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer

NCT04702737 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20200040
• Study Type: interventional
• Target: 41
• Locations: 8 countries
• Sites: 18

Brief Summary

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

Conditions

Neuroendocrine Prostate Cancer

Keywords

De novo or treatment emergent neuroendocrine prostate cancer; Non-canonical Notch ligand

Outcome Measures

Primary Outcomes (3)

• Number of Participants Who Experienced One or More Treatment-emergent Adverse Events (TEAEs)

  An adverse event (AE) was defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after the first dose of tarlatamab, and up to and including 47 days after the last dose of tarlatamab excluding the events reported after End of Study date. Clinically significant changes from baseline in vital signs, 12-lead electrocardiograms (ECGs) and clinical laboratory tests were also reported as TEAEs.

  Up to approximately 3 years

• Number of Participants Who Experienced One or More Treatment-related Adverse Events (TRAE)

  A TRAE was defined as a TEAE that per investigator review had a reasonable possibility of being caused by tarlatamab. Clinically significant changes from baseline in vital signs, 12-lead ECGs and clinical laboratory tests were also reported as TEAEs.

  Up to approximately 3 years

• Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

  A DLT was defined as any qualifying toxicity that was at least possibly related to tarlatamab with an onset within the first 28 days following first dose with either of the following criteria: 1. Grade 3 adverse event lasting more than 3 days (with the exception of fatigue and Grade 3 non-febrile neutropenia that improved to ≤ Grade 1 within 3 weeks including the use of growth factor support per neutropenia management guidelines); 2. ≥ Grade 4 adverse event regardless of duration (with the exception of grade 4 non-febrile neutropenia lasting less than or equal to 7 days including the use of growth factor support per neutropenia management guidelines).

  Up to 28 days

Secondary Outcomes (9)

• Objective Response Rate (ORR)

  Up to approximately 3 years

• Duration of Response (DOR)

  Up to approximately 3 years

• Radiographic Progression-free Survival (PFS)

  Up to approximately 3 years

• Overall Survival (OS)

  Up to approximately 3 years

• Disease Control Rate (DCR)

  Up to approximately 3 years

Study Arms (2)

Part 1: Dose Exploration

EXPERIMENTAL

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.

Drug: Tarlatamab

Part 2: Dose Expansion

EXPERIMENTAL

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

Drug: Tarlatamab

Interventions

Tarlatamab DRUG

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

Also known as: AMG 757

Part 1: Dose Exploration; Part 2: Dose Expansion

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amgen: lead

Study Sites (21)

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

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

San Francisco, California, 94158, United States

Location

Winship Cancer Institute of Emory University

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Community Health Network MD Anderson Cancer Center - North

Indianapolis, Indiana, 46250, United States

Location

Washington University

St Louis, Missouri, 63110-1093, United States

Location

Weill Cornell Medical College

New York, New York, 10021, United States

Location

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27103, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Medizinische Universitaet Graz

Graz, 8036, Austria

Location

Ordensklinikum Linz Elisabethinen

Linz, 4020, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Gustave Roussy

Villejuif, 94805, France

Location

Keio University Hospital

Shinjuku-ku, Tokyo, 160-8582, Japan

Location

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 40689871 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Interventions

AMG 757

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 11, 2021
• Study Start: June 10, 2021
• Primary Completion: July 22, 2024
• Study Completion: July 22, 2024
• Last Updated: September 12, 2025
• Results First Posted: September 12, 2025

Record last verified: 2025-08

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 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. 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.

Locations

JP (1); AU (2); BE (1); ES (1); US (10); FR (1); NL (1); GB (1)