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

NCT03319940 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 20160323
• Study Type: interventional
• Target: 269
• Locations: 12 countries
• Sites: 37

Brief Summary

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

Conditions

Small Cell Lung Carcinoma

Keywords

Half-Life Extended (HLE) Bispecific T cell engager (BiTE®); Delta-like protein 3 (DLL3); Tarlatamab; Oncology; Immunology

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (10)

• 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

Study Arms (6)

Part A

EXPERIMENTAL

Tarlatamab monotherapy

Drug: Tarlatamab

Part C

EXPERIMENTAL

Tarlatamab with Pembrolizumab

Drug: Tarlatamab; Drug: Pembrolizumab

Part D

EXPERIMENTAL

Tarlatamab with additional CRS mitigation strategies

Drug: Tarlatamab; Drug: CRS Mitigation Strategies

Part E

EXPERIMENTAL

Tarlatamab administration with 24-hour monitoring

Drug: Tarlatamab

Part F

EXPERIMENTAL

Tarlatamab administered in outpatient infusion centers with 8-hour monitoring Optional wearable digital device substudy (US sites only)

Drug: Tarlatamab

Part G

EXPERIMENTAL

Tarlatamab additional dosing schedule Optional wearable digital device substudy (US sites only)

Drug: Tarlatamab

Interventions

Tarlatamab DRUG

Tarlatamab is a Half-Life Extended (HLE) Bispecific T cell engager (BiTE®) targeting delta-like protein 3 (DLL3)

Part A; Part C; Part D; Part E; Part F; Part G

Pembrolizumab DRUG

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

Part C

CRS Mitigation Strategies DRUG

Participants will be treated with one of the CRS mitigation strategies.

Part D

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (39)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

John Hopkins Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Washington University

St Louis, Missouri, 63110-1093, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The Ohio State University Wexner Medical Center - Thoracic Oncology Clinic

Columbus, Ohio, 43210, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Medical Center Cancer Pavillion

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Medizinische Universitaet Graz

Graz, 8036, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97078, Germany

Location

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Wakayama Medical University Hospital

Wakayama, Wakayama, 641-8510, Japan

Location

Nederlands Kanker Instituut Antoni van Leeuwenhoekziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Maastricht Universitair Medisch Centrum

Maastricht, 6229 HX, Netherlands

Location

Biokinetica SA

Józefów, 05-410, Poland

Location

Europejskie Centrum Zdrowia Otwock Szpital imienia Fryderyka Chopina

Otwock, 05-400, Poland

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Centre Hospitalier Universitaire Vaudois

Lausanne, 1011, Switzerland

Location

Kantonsspital St Gallen

Sankt Gallen, 9007, Switzerland

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

Tri-Service General Hospital

Taipei, 11490, Taiwan

Location

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 31215500 BACKGROUND

• Dowlati A, Hummel HD, Champiat S, Olmedo ME, Boyer M, He K, Steeghs N, Izumi H, Johnson ML, Yoshida T, Bouchaab H, Borghaei H, Felip E, Jost PJ, Gadgeel S, Chen X, Yu Y, Martinez P, Parkes A, Paz-Ares L. Sustained Clinical Benefit and Intracranial Activity of Tarlatamab in Previously Treated Small Cell Lung Cancer: DeLLphi-300 Trial Update. J Clin Oncol. 2024 Oct 10;42(29):3392-3399. doi: 10.1200/JCO.24.00553. Epub 2024 Aug 29.

  PMID: 39208379 BACKGROUND

• Paz-Ares L, Champiat S, Lai WV, Izumi H, Govindan R, Boyer M, Hummel HD, Borghaei H, Johnson ML, Steeghs N, Blackhall F, Dowlati A, Reguart N, Yoshida T, He K, Gadgeel SM, Felip E, Zhang Y, Pati A, Minocha M, Mukherjee S, Goldrick A, Nagorsen D, Hashemi Sadraei N, Owonikoko TK. Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study. J Clin Oncol. 2023 Jun 1;41(16):2893-2903. doi: 10.1200/JCO.22.02823. Epub 2023 Jan 23.

  PMID: 36689692 BACKGROUND

• Chiang AC, Olmedo Garcia ME, Carlisle JW, Dowlati A, Reguart N, Felip E, Jost PJ, Steeghs N, Stec R, Gadgeel SM, Loong HH, Jiang W, Hamidi A, Parkes A, Paz-Ares L. Safety of tarlatamab with 6-8-h outpatient versus 48-h inpatient monitoring during cycle 1: DeLLphi-300 phase 1 substudy. ESMO Open. 2025 Apr;10(4):104538. doi: 10.1016/j.esmoop.2025.104538. Epub 2025 Apr 4.

  PMID: 40187110 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Bites and Stings; Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: The patient, investigator, investigative staff, medical monitor and care provider will not be masked for the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: This is an open-label, ascending, multiple doses, phase 1 study evaluating tarlatamab monotherapy, in combination with anti-PD1 therapy and with additional CRS mitigation strategies in participants with SCLC. The dose exploration phases of the study will estimate the maximum tolerated dose (MTD) or Recommended Phase 2 Dose (RP2D) of tarlatamab either as monotherapy or in combination with pembrolizumab. This will be followed by dose expansion phase to confirm RP2D and to obtain further safety and efficacy data.

Study Record Dates

• First Submitted: October 5, 2017
• First Posted: October 24, 2017
• Study Start: December 26, 2017
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

NL (2); PL (2); US (15); DE (1); ES (5); CH (2); GB (1); AU (1); JP (3); TW (3); FR (1); HK (1)