First-Line Tarlatamab in Combination With Carboplatin, Etoposide, and PD-L1 Inhibitor in Subjects With Extensive Stage Small Cell Lung Cancer (ES-SCLC)

A Phase 1b Study Evaluating the Safety and Efficacy of First-Line Tarlatamab in Combination With Carboplatin, Etoposide, and PD-L1 Inhibitor in Subjects With Extensive Stage Small Cell Lung Cancer

This is a phase 1b study to assess the safety and tolerability of tarlatamab in combination with programmed death ligand (PD-L1) inhibition with and without chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Extensive Stage Small Cell Lung Cancer
• Intervention / Treatment: Drug: Tarlatamab; Drug: Carboplatin; Drug: Etoposide; Drug: Atezolizumab; Drug: Durvalumab

• Study Type: Interventional
• Enrollment (Estimated): 340
• 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
• Belgium
  • Edegem, Belgium, 2650
    • Recruiting
    • Universitair Ziekenhuis Antwerpen
  • Gent, Belgium, 9000
    • Recruiting
    • Algemeen Ziekenhuis Maria Middelares
  • Hasselt, Belgium, 3500
    • Recruiting
    • Jessa Ziekenhuis - Campus Virga Jesse
  • Roeselare, Belgium, 8800
    • Recruiting
    • AZ Delta Campus Rumbeke
• Canada
  • Quebec, Canada, G1R 2J6
    • Recruiting
    • CHU de Quebec Hopital de l Enfant Jesus
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
• Denmark
  • Kobenhavn, Denmark, 2100
    • Terminated
    • Rigshospitalet
• France
  • Lyon cedex 8, France, 69373
    • Recruiting
    • Centre Léon Bérard
  • Saint Herblain, France, 44800
    • Recruiting
    • Centre Hospitalier Universitaire de Nantes, Hôpital Nord Laënnec
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Germany
  • Dresden, Germany, 01307
    • Recruiting
    • Universitaetsklinikum Dresden
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum Essen
  • Freiburg, Germany, 79106
    • Recruiting
    • Universitaetsklinikum Freiburg
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Medical Center
  • Jerusalem, Israel, 9112001
    • Recruiting
    • Hadassah Ein-Kerem Medical Center
  • Petah Tikva, Israel, 4941492
    • Recruiting
    • Rabin Medical Center
  • Ramat Gan, Israel, 5265601
    • Recruiting
    • Sheba Medical Center
• Italy
  • Catanzaro, Italy, 88100
    • Recruiting
    • Azienda Ospedaliera Universitaria Renato Dulbecco
  • Monza (MB), Italy, 20900
    • Recruiting
    • Fondazione IRCCS San Gerardo dei Tintori
  • Rome, Italy, 00144
    • Recruiting
    • Istituto Nazionale Tumori Regina Elena
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Tokyo
    • Koto-ku, Tokyo, Japan, 135-8550
      • Recruiting
      • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
• Netherlands
  • Groningen, Netherlands, 9713 GZ
    • Recruiting
    • Universitair Medisch Centrum Groningen
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 De Octubre
  • Cataluña
    • Badalona, Cataluña, Spain, 08916
      • Recruiting
      • Institut Catala d Oncologia Badalona Hospital Universitari Germans Trias i Pujol
    • Barcelona, Cataluña, Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d Hebron
• Switzerland
  • Basel, Switzerland, 4031
    • Recruiting
    • Universitaetsspital Basel
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital Bern
• Taiwan
  • Tainan, Taiwan, 70403
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • University of Southern California, Norris Comprehensive Cancer Center
  • Delaware
    • Newark, Delaware, United States, 19713
      • Recruiting
      • Christiana Care Health Services
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Health System
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • New York University Langone Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • The University of North Carolina at Chapel Hill
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Recruiting
      • Avera Cancer Institute
  • Washington
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Cancer Institute Medical Oncology
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University Health Sciences Center

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 same time of signing the informed consent.
• Histologically or cytologically confirmed Extensive Stage Small Cell Lung Cancer (ES-SCLC) and no prior systemic treatment for ES-SCLC.
• Participants with prior treatment for limited-stage SCLC (LS-SCLC) are permitted.
• Eastern Cooperative Oncology Group (ECOG) 0 to 1.
• Participants with treated asymptomatic 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.
• Major surgery within 28 days of study day 1.
• Untreated or symptomatic brain metastases and leptomeningeal disease.
• Participants who experienced recurrent grade 2 pneumonitis or severe or life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.
• History of immune-related colitis.
• History or 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 study treatment.
• Participants 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 study treatment
• Participant has known active infection requiring parenteral antibiotic treatment. Upon completion of parenteral antibiotics and resolution of symptoms, the participant may be considered eligible for the study from an infection standpoint
• NOTE: Simple urinary tract infections and uncomplicated bacterial pharyngitis are permitted if responding to an active treatment and after consultation with Medical Monitor. Participants requiring oral antibiotics who have been afebrile for >24 hours, have no leukocytosis, nor clinical signs of infection are eligible. Screening for chronic infectious conditions is not required.
• History of hypophysitis or pituitary dysfunction.
• History of solid organ transplantation or allogeneic hematopoietic stem cell transplantation.
• Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type I diabetes, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted.

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

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Dose Exploration Combination Regimen 1; Tarlatamab+Atezolizumab+Carboplatin+Etoposide	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Carboplatin; Carboplatin will be administered as an intravenous (IV) infusion.; Drug: Etoposide; Etoposide will be administered as an intravenous (IV) infusion.; Drug: Atezolizumab; Atezolizumab will be administered as an intravenous (IV) infusion.; Other Names: Tecentriq
Experimental: Part 2: Dose Exploration Combination Regimen 2; Tarlatamab+Atezolizumab+Carboplatin+Etoposide	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Carboplatin; Carboplatin will be administered as an intravenous (IV) infusion.; Drug: Etoposide; Etoposide will be administered as an intravenous (IV) infusion.; Drug: Atezolizumab; Atezolizumab will be administered as an intravenous (IV) infusion.; Other Names: Tecentriq
Experimental: Part 3: Dose Exploration Combination Regimen 3; Tarlatamab+Atezolizumab+Carboplatin+Etoposide	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Carboplatin; Carboplatin will be administered as an intravenous (IV) infusion.; Drug: Etoposide; Etoposide will be administered as an intravenous (IV) infusion.; Drug: Atezolizumab; Atezolizumab will be administered as an intravenous (IV) infusion.; Other Names: Tecentriq
Experimental: Part 4: Dose Expansion; Expansion of Part 1, Part 2, or Part 3 with Atezolizumab	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Carboplatin; Carboplatin will be administered as an intravenous (IV) infusion.; Drug: Etoposide; Etoposide will be administered as an intravenous (IV) infusion.; Drug: Atezolizumab; Atezolizumab will be administered as an intravenous (IV) infusion.; Other Names: Tecentriq
Experimental: Part 5: Dose Exploration Maintenance; Tarlatamab+Atezolizumab	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Atezolizumab; Atezolizumab will be administered as an intravenous (IV) infusion.; Other Names: Tecentriq
Experimental: Part 6: Dose Expansion Maintenance; Expansion of Part 5 with Atezolizumab	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Atezolizumab; Atezolizumab will be administered as an intravenous (IV) infusion.; Other Names: Tecentriq
Experimental: Part 7: Dose Expansion; Expansion of Part 1, 2, or 3 with Durvalumab	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Carboplatin; Carboplatin will be administered as an intravenous (IV) infusion.; Drug: Etoposide; Etoposide will be administered as an intravenous (IV) infusion.; Drug: Durvalumab; Durvalumab will be administered as an intravenous (IV) infusion.
Experimental: Part 8: Dose Expansion Maintenance; Expansion of Part 5 with Durvalumab	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Durvalumab; Durvalumab will be administered as an intravenous (IV) infusion.
Experimental: Part 9: Dose Expansion Maintenance; Expansion with Tarlatamab+Durvalumab	Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757; Drug: Durvalumab; Durvalumab will be administered as an intravenous (IV) infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with a Dose Limiting Toxicity (DLT)	24 months
Number of Participants with Treatment-emergent Adverse Events (TEAE)	24 months
Number of Participants with Treatment-related Adverse Events	24 months
Number of Participants with Clinically Significant Changes in Vital Signs	24 months
Number of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Measurements	24 months
Number of Participants with Clinically Significant Changes in Clinical Laboratory Tests	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)		24 months
6-month Progression-free Survival (PFS)		24 months
Objective Response (OR)	Per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	24 months
Duration of Response (DOR)		24 months
Disease Control Rate(DCR)		24 months
Serum Concentration of Tarlatamab		24 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2022
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Lung Cancer; Inmunotherapy; Extensive Stage Small Cell Lung Cancer; ES-SCLC; SCLC; Immunooncology; DLL3; AMG 757; Bi-Specific T-Cell Engager; BiTE; Inmuno-oncology; Delta Like Protein 3
• 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; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Carboplatin; Etoposide; Durvalumab; Atezolizumab; AMG 757
• Other Study ID Numbers: 20200469; 2021-005462-17 (EudraCT Number)

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