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

• ClinicalTrials.gov Identifier: NCT04702737
• Recruitment Status: Active, not recruiting
• First Posted: January 11, 2021
• Last Update Posted: March 25, 2024
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: January 7, 2021
• First Posted Date: January 11, 2021
• Last Update Posted Date: March 25, 2024
• Actual Study Start Date: June 10, 2021
• Estimated Primary Completion Date: August 23, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 7, 2021)

• Number of Participants who Experience One or More Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 to 12 months ]
• Number of Participants who Experience One or More Treatment-related Adverse Events [ Time Frame: Day 1 to 12 months ]
• Number of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs [ Time Frame: Baseline to 12 months ]
• Number of Participants who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements [ Time Frame: Baseline to 12 months ]
• Number of Participants who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests [ Time Frame: Baseline to 12 months ]
• Number of Participants who Experience Dose Limiting Toxicities (DLTs) [ Time Frame: Baseline to 12 months ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 29, 2021)

• Objective Response (OR) [ Time Frame: Baseline to 12 months ]
  OR will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications.
• Duration of Response (DOR) [ Time Frame: Baseline to 12 months ]
• Progression-free Survival (PFS) [ Time Frame: Baseline to 12 months ]
• Overall Survival (OS) [ Time Frame: Baseline to 12 months ]
• Disease Control Rate (DCR) [ Time Frame: Baseline to 12 months ]
• Maximum Serum Concentration (Cmax) of Tarlatamab [ Time Frame: Baseline to 12 months ]
• Minimum Serum Concentration (Cmin) of Tarlatamab [ Time Frame: Baseline to 12 months ]
• Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of Tarlatamab [ Time Frame: Baseline to 12 months ]
• Accumulation Ratio of Tarlatamab [ Time Frame: Baseline to 12 months ]
• Half-life (t1/2) of Tarlatamab [ Time Frame: Baseline to 12 months ]

Original Secondary Outcome Measures (submitted: January 7, 2021)

• Objective Response (OR) [ Time Frame: Baseline to 12 months ]
  OR will be assessed per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications.
• Duration of Response (DOR) [ Time Frame: Baseline to 12 months ]
• Progression-free Survival (PFS) [ Time Frame: Baseline to 12 months ]
• Overall Survival (OS) [ Time Frame: Baseline to 12 months ]
• Maximum Serum Concentration (Cmax) of AMG 757 [ Time Frame: Baseline to 12 months ]
• Minimum Serum Concentration (Cmin) of AMG 757 [ Time Frame: Baseline to 12 months ]
• Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 757 [ Time Frame: Baseline to 12 months ]
• Accumulation Ratio of AMG 757 [ Time Frame: Baseline to 12 months ]
• Half-life (t1/2) of AMG 757 [ Time Frame: Baseline to 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of AMG 757 in Participants With Neuroendocrine Prostate Cancer
• Official Title: 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
• Brief Summary: To evaluate the safety and tolerability of Tarlatamab and will determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neuroendocrine Prostate Cancer

Intervention

Drug: Tarlatamab

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

Other Name: AMG 757

Study Arms

• 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.
  Intervention: Drug: Tarlatamab
• Experimental: Part 2: Dose Expansion
  Participants will receive the RP2D/MTD identified in Part 1 (dose exploration) of the study.
  Intervention: Drug: Tarlatamab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 1, 2023): 41
• Original Estimated Enrollment (submitted: January 7, 2021): 60
• Estimated Study Completion Date: August 23, 2025
• Estimated Primary Completion Date: August 23, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, France, Japan, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04702737
• Other Study ID Numbers: 20200040
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (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.
• URL: http://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: March 2024