We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04702737
Recruitment Status : Recruiting
First Posted : January 11, 2021
Last Update Posted : May 25, 2023
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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
Neuroendocrine Prostate Cancer Drug: Tarlatamab Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 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 Tarlatamab in Subjects With De Novo or Treatment Emergent Neuroendocrine Prostate Cancer
Actual Study Start Date : June 10, 2021
Estimated Primary Completion Date : April 15, 2026
Estimated Study Completion Date : April 15, 2027

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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 Name: 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 Name: AMG 757
Experimental: Part 2: Biomarker Expansion
Participants who test delta-like protein 3 (DLL3) positive will receive a dose of tarlatamab determined by Amgen study 20160323 (NCT03319940).
 Drug: Tarlatamab
Tarlatamab will be administered as an intravenous (IV) infusion.
Other Name: AMG 757


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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

Secondary Outcome Measures :
  1. 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.

  2. Duration of Response (DOR) [ Time Frame: Baseline to 12 months ]
  3. Progression-free Survival (PFS) [ Time Frame: Baseline to 12 months ]
  4. Overall Survival (OS) [ Time Frame: Baseline to 12 months ]
  5. Disease Control Rate (DCR) [ Time Frame: Baseline to 12 months ]
  6. Maximum Serum Concentration (Cmax) of Tarlatamab [ Time Frame: Baseline to 12 months ]
  7. Minimum Serum Concentration (Cmin) of Tarlatamab [ Time Frame: Baseline to 12 months ]
  8. Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of Tarlatamab [ Time Frame: Baseline to 12 months ]
  9. Accumulation Ratio of Tarlatamab [ Time Frame: Baseline to 12 months ]
  10. Half-life (t1/2) of Tarlatamab [ Time Frame: Baseline to 12 months ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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 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.
  • 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

Inclusion Criteria (Part 2: Biomarker Expansion):

Participants are eligible to be included in Part 2: Biomarker Expansion of the study only if all of the following criteria apply:

  • Participants aged ≥ 18 years at time of signing the informed consent.
  • Metastatic de novo or treatment-emergent NEPC not amenable to curative treatment with the following characteristics:
  • Neuroendocrine prostate carcinoma defined as either poorly differentiated carcinoma with similar histology as small cell lung cancer (SCLC), mixed tumors with both prostate adenocarcinoma and small cell morphologies, or cancers with high clinical or pathological suspicion for NEPC.
  • Tumor must be positive for DLL3 expression according to central pathology review.
  • Progressed on at least 1 line of prior systemic treatment with a platinum containing agent
  • Exception: participants may also be included if the aforementioned therapeutic options were medically not appropriate for them. In these cases, the reason(s) why required prior therapies were medically not appropriate should be documented in the participant's electronic case report form (eCRF).
  • Measurable disease per RECIST 1.1 per PCWG3 modifications
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2
  • Minimum life expectancy of 12 weeks, in the opinion of the investigator
  • Participants with treated brain metastases are eligible provided they meet the following criteria:
  • Definitive treatment was completed at least 2 weeks prior to the first planned dose of study treatment (stereotactic radiosurgery at least 7 days prior to first planned dose of study treatment)
  • At least 7 days prior to treatment: any central nervous system (CNS) disease is clinically stable, participant is off steroids for CNS disease (unless steroids are indicated for a reason unrelated to CNS disease), and participant is off or on stable doses of anti-epileptic drugs.

Exclusion Criteria (Part 1: Dose Exploration, Part 2: Dose Expansion and Part 2: Biomarker 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 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 12 months
    • 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 protein 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).
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04702737


Contacts
Layout table for location contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
Show Show 21 study locations
Sponsors and Collaborators
Amgen
Investigators
Layout table for investigator information
Study Director: MD Amgen
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT04702737    
Other Study ID Numbers: 20200040
First Posted: January 11, 2021    Key Record Dates
Last Update Posted: May 25, 2023
Last Verified: May 2023
Individual Participant Data (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
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
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

Layout table for additional information
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:
Layout table for MeSH terms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
 Genital Diseases
Urogenital Diseases
Prostatic Diseases
Male Urogenital Diseases
AMG 757
Antineoplastic Agents