A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer (DeLLpro-300)

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Delta-like Protein 3 Half-life Extended Bispecific T-cell Engager AMG 757 in Subjects With De Novo or Treatment Emergent Neuroendocrine Prostate Cancer

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

Study Overview

• Status: Completed
• Conditions: Neuroendocrine Prostate Cancer
• Intervention / Treatment: Drug: Tarlatamab

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Chris OBrien Lifehouse
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
• Austria
  • Graz, Austria, 8036
    • Medizinische Universitaet Graz
  • Linz, Austria, 4020
    • Ordensklinikum Linz Elisabethinen
  • Salzburg, Austria, 5020
    • Landeskrankenhaus Salzburg
• Belgium
  • Ghent, Belgium, 9000
    • Universitair Ziekenhuis Gent
• France
  • Villejuif, France, 94805
    • Gustave Roussy
• Japan
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 160-8582
      • Keio university hospital
• Netherlands
  • Rotterdam, Netherlands, 3015 GD
    • Erasmus Medisch Centrum
• Spain
  • Catalonia
    • Barcelona, Catalonia, Spain, 08036
      • Hospital Clinic i Provincial de Barcelona
• United Kingdom
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona
  • California
    • San Francisco, California, United States, 94158
      • University of California at San Francisco Helen Diller Family Comprehensive Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute of Emory University
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Health Network MD Anderson Cancer Center - North
  • Missouri
    • St Louis, Missouri, United States, 63110-1093
      • Washington University
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Wake Forest University Health Sciences
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (Part 1: Dose Exploration and Part 2: Dose Expansion):

• 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 (Part 1: Dose Exploration and Part 2: Dose Expansion):

• 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757
Experimental: Part 2: Dose Expansion; Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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);; ≥ 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	OR was assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications. OR was defined as best overall response of partial response (PR) or complete response (CR) per RECIST 1.1, confirmed by an assessment at least 4 weeks later. Participants who did not experience a PR/CR or did not have any follow-up tumor assessments were regarded as non-responders. ORR was defined as the percentage of participants with a best overall response of confirmed CR or PR per RECIST 1.1. The percentage of participants with an OR was summarized along with the Clopper-Pearson (Clopper and Pearson, 1934) exact 95% confidence interval (CI). The result reported was evaluated by central reviewer assessment.	Up to approximately 3 years
Duration of Response (DOR)	DOR was defined as the time from the date of an initial objective response to the earlier of progressive disease or death for participants with an objective response per RECIST 1.1. DOR was assessed per RECIST 1.1 with PCWG3 modifications. The distribution of DOR was summarized using the Kaplan-Meier (KM) method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method. The result reported was evaluated by central reviewer assessment.	Up to approximately 3 years
Radiographic Progression-free Survival (PFS)	Radiographic PFS was defined as the interval from the first dose of tarlatamab to the earlier of a radiographic progression or death from any cause. Radiographic PFS was assessed per RECIST 1.1 with PCWG3 modifications. The distribution of radiographic PFS was summarized using the KM method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method. The result reported was evaluated by central reviewer assessment.	Up to approximately 3 years
Overall Survival (OS)	OS was defined as the time from the start of treatment until event of death due to any cause. The distribution of OS was summarized using the KM method with CI calculated using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method.	Up to approximately 3 years
Disease Control Rate (DCR)	DCR was defined as the percentage of participants with a best overall response of confirmed response (CR/PR) or stable disease (SD) as per RECIST 1.1. The DCR was assessed per RECIST 1.1. The percentage of participants with disease control with corresponding exact 95% CI was calculated using the Clopper-Pearson (Clopper and Pearson, 1934) method. The result reported was evaluated by central reviewer assessment.	Up to approximately 3 years
Maximum Serum Concentration (Cmax) of Tarlatamab	Pharmacokinetic (PK) parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.	Cycle 2 Day 1 and Day 15: Predose, end of infusion (EOI), 2, 6, 24, 48, 96 and 168 hours after EOI
Tarlatamab Concentration at the End of a Dosing Interval or Before Planned Next Dose (Ctrough)	PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.	Cycle 2 Day 15: Predose
Area Under the Concentration-time Curve Over the Dosing Interval From Time 0 to 336 Hours (AUC336) of Tarlatamab	PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.	Cycle 2 Day 1 and Day 15: Predose, EOI, 2, 6, 24, 48, 96, 168, and 336 hours after EOI
Terminal Phase Elimination Half-life (t1/2,z) of Tarlatamab	PK parameters of tarlatamab were determined from the time concentration profile using standard non-compartmental approaches and considering the profile over the complete sampling interval. The result for this endpoint is given for cycle 2 only.	Cycle 2 Day 15: Predose, EOI, 2, 6, 24, 48, 96 and 168 hours after EOI

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

General Publications

• 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 Jul 21. doi: 10.1158/1078-0432.CCR-25-1211. Online ahead of print.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2021
• Primary Completion (Actual): July 22, 2024
• Study Completion (Actual): July 22, 2024

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Estimated): September 12, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: De novo or treatment emergent neuroendocrine prostate cancer; Non-canonical Notch ligand
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Antineoplastic Agents; AMG 757
• Other Study ID Numbers: 20200040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No