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A Study of Tarlatamab (AMG 757) in Participants With Neuroendocrine Prostate Cancer

Sponsor
Amgen (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04702737
Collaborator
(none)
60
Enrollment
20
Locations
2
Arms
58
Anticipated Duration (Months)
3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 10, 2021
Anticipated Primary Completion Date :
Oct 3, 2023
Anticipated Study Completion Date :
Apr 10, 2026

Arms and Interventions

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 received the recommended phase 2 dose (RP2D) identified in Part 1 (dose exploration) of the study.

    Drug: Tarlatamab
    Tarlatamab will be administered as an intravenous (IV) infusion.
    Other Names:
  • AMG 757

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants who Experience One or More Treatment-emergent Adverse Events (TEAEs) [Day 1 to 12 months]

    2. Number of Participants who Experience One or More Treatment-related Adverse Events [Day 1 to 12 months]

    3. Number of Participants who Experience a Clinically Significant Change from Baseline in Vital Signs [Baseline to 12 months]

    4. Number of Participants who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements [Baseline to 12 months]

    5. Number of Participants who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests [Baseline to 12 months]

    6. Number of Participants who Experience Dose Limiting Toxicities (DLTs) [Baseline to 12 months]

    Secondary Outcome Measures

    1. Objective Response (OR) [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.

    2. Duration of Response (DOR) [Baseline to 12 months]

    3. Progression-free Survival (PFS) [Baseline to 12 months]

    4. Overall Survival (OS) [Baseline to 12 months]

    5. Disease Control Rate (DCR) [Baseline to 12 months]

    6. Maximum Serum Concentration (Cmax) of Tarlatamab [Baseline to 12 months]

    7. Minimum Serum Concentration (Cmin) of Tarlatamab [Baseline to 12 months]

    8. Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of Tarlatamab [Baseline to 12 months]

    9. Accumulation Ratio of Tarlatamab [Baseline to 12 months]

    10. Half-life (t1/2) of Tarlatamab [Baseline to 12 months]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Male
    Accepts Healthy Volunteers:
    No
    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 histological, 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.

    • For participants with treatment-emergent NEPC or de novo NEPC with histologic evidence of prostate cancer with neuroendocrine differentiation.

    • 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 is permitted; participants on a stable bisphosphonate or denosumab for ≥ 30 days 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 DLL3-targeted therapy may be eligible if discussed with Amgen medical monitor prior to enrollment

    • History or evidence of SARS-COV2 infection unless agreed upon with Medical Monitor and with no acute symptoms of COVID19 disease within 14 days prior to first dose of IP (counted from day of positive test for asymptomatic subjects).

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic Arizona Phoenix Arizona United States 85054
    2 University of California at San Francisco Helen Diller Family Comprehensive Cancer Center San Francisco California United States 94158
    3 Winship Cancer Institute of Emory University Atlanta Georgia United States 30322
    4 University of Chicago Chicago Illinois United States 60637
    5 Community Health Network Indianapolis Indiana United States 46250
    6 Washington University Saint Louis Missouri United States 63110-1093
    7 Weill Cornell Medical College New York New York United States 10021
    8 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27103
    9 University of Texas MD Anderson Cancer Center Houston Texas United States 77030
    10 Chris OBrien Lifehouse Camperdown New South Wales Australia 2050
    11 Peter MacCallum Cancer Centre Melbourne Victoria Australia 3000
    12 Medizinische Universitaet Graz Graz Austria 8036
    13 Ordensklinikum Linz Elisabethinen Linz Austria 4020
    14 Landeskrankenhaus Salzburg Salzburg Austria 5020
    15 Universitair Ziekenhuis Gent Gent Belgium 9000
    16 Gustave Roussy Villejuif Cedex France 94805
    17 Keio University Hospital Shinjuku-ku Tokyo Japan 160-8582
    18 Erasmus Medisch Centrum Rotterdam Netherlands 3015 GD
    19 Hospital Clinic i Provincial de Barcelona Barcelona Cataluña Spain 08036
    20 Royal Marsden Hospital Sutton United Kingdom SM2 5PT

    Sponsors and Collaborators

    • Amgen

    Investigators

    • Study Director: MD, Amgen

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Amgen
    ClinicalTrials.gov Identifier:
    NCT04702737
    Other Study ID Numbers:
    • 20200040
    First Posted:
    Jan 11, 2021
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Amgen
    De novo or treatment emergent neuroendocrine prostate cancer
    Delta-like protein 3 (DLL3)
    Non-canonical Notch ligand
    Additional relevant MeSH terms:
    Prostatic Neoplasms

    Study Results

    No Results Posted as of Aug 12, 2022