Study Evaluating Safety, Tolerability and Pharmacokinetics (PK) of Tarlatamab in Adults With Small Cell Lung Cancer (SCLC)

A Phase 1 Study Evaluating the Safety, Tolerability and Pharmacokinetics of Tarlatamab in Subjects With Small Cell Lung Cancer (DeLLphi-300)

A study to assess the safety, tolerability, and PK of tarlatamab in participants with SCLC

Study Overview

• Status: Recruiting
• Conditions: Small Cell Lung Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Tarlatamab; Drug: CRS Mitigation Strategies

Detailed Description

This is an open-label, ascending, multiple doses, phase 1 study evaluating tarlatamab monotherapy, in combination with anti-PD1 therapy and with additional cytokine release syndrome (CRS) mitigation strategies. Tarlatamab will be administered as a short term intravenous (IV) infusion in participants with SCLC. Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)

• Study Type: Interventional
• Enrollment (Estimated): 392
• Phase: Phase 1

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris OBrien Lifehouse
• Austria
  • Graz, Austria, 8036
    • Recruiting
    • Medizinische Universitaet Graz
  • Salzburg, Austria, 5020
    • Terminated
    • Landeskrankenhaus Salzburg
• France
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Germany
  • Wuerzburg, Germany, 97078
    • Recruiting
    • Universitaetsklinikum Wuerzburg
• Hong Kong
  • Shatin, New Territories, Hong Kong
    • Recruiting
    • Prince of Wales Hospital
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital
  • Wakayama
    • Wakayama-shi, Wakayama, Japan, 641-8510
      • Recruiting
      • Wakayama Medical University Hospital
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Recruiting
    • Nederlands Kanker Instituut Antoni van Leeuwenhoekziekenhuis
  • Maastricht, Netherlands, 6229 HX
    • Completed
    • Maastricht Universitair Medisch Centrum
• Poland
  • Jozefow, Poland, 05-410
    • Recruiting
    • Biokinetica SA
  • Otwock, Poland, 05-400
    • Recruiting
    • Europejskie Centrum Zdrowia Otwock Szpital imienia Fryderyka Chopina
• Spain
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Cataluña
    • Barcelona, Cataluña, Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d Hebron
    • Barcelona, Cataluña, Spain, 08036
      • Recruiting
      • Hospital Clinic i Provincial de Barcelona
• Switzerland
  • Lausanne, Switzerland, 1011
    • Recruiting
    • Centre Hospitalier Universitaire Vaudois
  • Sankt Gallen, Switzerland, 9007
    • Recruiting
    • Kantonsspital St Gallen
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Recruiting
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taipei, Taiwan, 11490
    • Recruiting
    • Tri-Service General Hospital
  • Taoyuan, Taiwan, 33305
    • Recruiting
    • Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • Christie Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • Completed
      • City of Hope National Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale New Haven Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • Terminated
      • Moffitt Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Recruiting
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Recruiting
      • John Hopkins Sidney Kimmel Comprehensive Cancer Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1093
      • Recruiting
      • Washington University
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • University Hospitals Cleveland Medical Center
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • Terminated
      • University of Pittsburgh Medical Center Cancer Pavillion
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participant has provided informed consent prior to initiation of any study-specific activities/procedures
• Age greater than or equal to 18 years old at the time of signing the informed consent
• Histologically or cytologically confirmed SCLC. For parts A, C, D, E, F, and G: relapsed/refractory small cell lung cancer (R/R SCLC) who progressed or recurred following platinum-based regimen
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• 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 prior to first dose of tarlatamab with exceptions
• Major surgery within 28 days of first dose tarlatamab
• Untreated (includes new lesions or progression in previously treated lesions) or symptomatic brain metastases and leptomeningeal disease (regardless of symptomatic or not).
• Prior anti-cancer therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and first dose of tarlatamab with the following exceptions: participants who received conventional chemotherapy are eligible if at least 14 days have elapsed and if all treatment-related toxicity has been resolved to Grade less than or equal to 1; and prior palliative radiotherapy must have been completed at least 7 days before the first dose of tarlatamab
• Participants who experienced severe, life-threatening or recurrent (Grade 2 or higher) immune-mediated AEs or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immune-oncology agents
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of tarlatamab
• Part C only: history of solid organ transplantation or active autoimmune disease that has required systemic treatment within the past 2 years
• Participant with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of investigational product administration

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A; Tarlatamab monotherapy	Drug: Tarlatamab; Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
Experimental: Part C; Tarlatamab with Pembrolizumab	Drug: Pembrolizumab; Pembrolizumab is a potent humanized IgG4 monoclonal antibody (mAb) with high specificity of binding to the PD-1 receptor, thus inhibiting its interaction with PD-L1 and PD-L2; Drug: Tarlatamab; Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
Experimental: Part D; Tarlatamab with additional CRS mitigation strategies	Drug: Tarlatamab; Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3); Drug: CRS Mitigation Strategies; Participants will be treated with one of the CRS mitigation strategies.
Experimental: Part E; Tarlatamab administration with 24-hour monitoring	Drug: Tarlatamab; Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
Experimental: Part F; Tarlatamab administered in outpatient infusion centers with 8-hour monitoring Optional wearable digital device substudy (US sites only)	Drug: Tarlatamab; Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)
Experimental: Part G; Tarlatamab additional dosing schedule Optional wearable digital device substudy (US sites only)	Drug: Tarlatamab; Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of participants with dose limiting toxicities (DLT) for all indications	6 months
Number of participants with treatment-emergent adverse events (AEs) for all indications	4 years
Number of participants with treatment-related AEs for all indications	4 years
Number of participants with clinically significant changes in vital signs for all indications	4 years
Number of participants with significant changes in electrocardiogram (ECG) for all indications	4 years
Number of participants with significant changes in physical examinations for all indications	4 years
Number of participants with significant changes in clinical laboratory tests for all indications	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
9-month Progression-Free Survival (PFS) for all indications		9 months
9-month Overall Survival (OS) for all indications		9 months
Maximum observed concentration (Cmax) following intravenous administration for all indications		4 years
Minimum observed concentration (Cmin) following intravenous administration for all indications		4 years
Area under the concentration-time curve (AUC) over the 2 week dosing interval for all indications		4 years
Accumulation following multiple dosing for all indications		4 years
Half-life (t1/2) following intravenous administration for all indications		4 years
Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Only for parts A, D, E, F, and G	4 years
Duration of Response (DOR) for all indications		4 years
Time to Response (TTR)		4 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Owen DH, Giffin MJ, Bailis JM, Smit MD, Carbone DP, He K. DLL3: an emerging target in small cell lung cancer. J Hematol Oncol. 2019 Jun 18;12(1):61. doi: 10.1186/s13045-019-0745-2.

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2017
• Primary Completion (Estimated): October 18, 2024
• Study Completion (Estimated): October 18, 2025

Study Registration Dates

• First Submitted: October 5, 2017
• First Submitted That Met QC Criteria: October 19, 2017
• First Posted (Actual): October 24, 2017

Study Record Updates

• Last Update Posted (Actual): June 13, 2024
• Last Update Submitted That Met QC Criteria: June 11, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Immunology; Oncology; Delta-like protein 3 (DLL3); Tarlatamab; Half-Life Extended (HLE) Bispecific T cell engager (BiTE®)
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab
• Other Study ID Numbers: 20160323

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