A Phase 2 Study of Tarlatamab in Patients With Small Cell Lung Cancer (SCLC)

NCT05060016 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 202004912024-511837-37
• Study Type: interventional
• Target: 222
• Locations: 18 countries
• Sites: 80

Brief Summary

The main aim of this study is to:

• evaluate safety and efficacy (per Response Evaluation Criteria in Solid Tumors version 1.1 \[RECIST 1.1\] by investigator) of 2 dose levels of tarlatamab for Part 1 only
• evaluate anti-tumor activity of tarlatamab as determined by objective response rate (ORR) per RECIST 1.1 by blinded independent central review (BICR) for Part 1 and 2
• evaluate safety of reduced mandatory monitoring period in Cycle 1 at selected dose of tarlatamab for Part 3

Conditions

Relapsed/Refractory Small Cell Lung Cancer

Keywords

Small Cell Lung Cancer; SCLC; AMG 757; Tarlatamab; IMDELLTRA^TM

Outcome Measures

Primary Outcomes (4)

• Part 1 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator

  Up to a maximum of 61 months

• Part 1 and Part 3 Only: Number of Participants who Experience One or More Treatment-emergent Adverse Events

  Up to a maximum of 61 months

• Part 1 Only: Serum Concentrations of Tarlatamab

  Up to a maximum of 24 months

• Part 1 and Part 2 Only: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)

  Up to a maximum of 61 months

Secondary Outcomes (13)

• Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)

  Up to a maximum of 73 months

• Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)

  Up to a maximum of 73 months

• Duration of Disease Control (DC) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)

  Up to a maximum of 73 months

• Progression-free Survival (PFS) Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Blinded Independent Central Review (BICR)

  Up to a maximum of 73 months

• Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by Investigator

  Up to a maximum of 73 months

Study Arms (4)

Part 1: Tarlatamab Low Dose

EXPERIMENTAL

Participants will receive the low dose of Tarlatamab.

Drug: Tarlatamab

Part 1: Tarlatamab High Dose

EXPERIMENTAL

Participants will receive the high dose of Tarlatamab.

Drug: Tarlatamab

Part 2: Dose Expansion

EXPERIMENTAL

Participants will receive the selected target dose of Tarlatamab based on findings in Part 1.

Drug: Tarlatamab

Part 3: Modified Monitoring Substudy

EXPERIMENTAL

Participants will receive the selected target dose of Tarlatamab based on findings in Part 1 with reduced Cycle 1 monitoring requirements.

Drug: Tarlatamab

Interventions

Tarlatamab DRUG

Intravenous (IV) infusion

Part 1: Tarlatamab High Dose; Part 1: Tarlatamab Low Dose; Part 2: Dose Expansion; Part 3: Modified Monitoring Substudy

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/assent prior to initiation of any study specific activities/procedures.
• Male and female participants ≥ 18 years of age (or legal adult age within country) at the time of signing the informed consent.
• Histologically or cytologically confirmed relapsed/refractory SCLC
• Participants who progressed or recurred following 1 platinum-based regimen and at least 1 other prior line of therapy.
• Participants willing to provide archived tumor tissue samples or willing to undergo pretreatment tumor biopsy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 1.
• Minimum life expectancy of 12 weeks.
• Measurable lesions as defined per RECIST 1.1 within 21 days prior to the first dose of tarlatamab.
• Participants with treated brain metastases are eligible provided they meet defined criteria.

You may not qualify if:

• Disease Related
• Untreated or symptomatic brain metastases and leptomeningeal disease.
• Has evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Participants who experienced recurrent pneumonitis (grade 2 or higher) or severe, life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents.
• Unresolved toxicity from prior anti-tumor therapy, defined as per protocol.
• Other Medical Conditions
• History of other malignancy within the past 2 years, with exceptions
• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association \> class II) within 12 months of first dose of tarlatamab.
• History of arterial thrombosis (eg, stroke or transient ischemic attack) within 12 months of first dose of tarlatamab.
• 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 tarlatamab.
• Presence of any indwelling line or drain.
• History of hypophysitis or pituitary dysfunction.
• Major surgery within 28 days of first dose of tarlatamab.
• History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Subject is eligible if no acute symptoms of coronavirus disease 2019 (COVID-19) within 14 days prior to first dose of tarlatamab (counted from day of positive test for asymptomatic subjects).
• Prior/Concomitant Therapy

Sponsors & Collaborators

• Amgen: lead

Study Sites (80)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Christiana Care Health Services

Newark, Delaware, 19713, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute

Atlanta, Georgia, 30332, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Dana Farber - Harvard Cancer Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Dartmouth Hitchcock Medical Center

Hanover, New Hampshire, 03756, United States

Location

Duke University Medical Center

Durham, North Carolina, 27705, United States

Location

Wake Forest Baptist Comprehensive Cancer Research Center

Winston-Salem, North Carolina, 27157, United States

Location

Oncology Hematology Care Inc

Cincinnati, Ohio, 45242, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, 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

West Virginia University Health Sciences Center

Morgantown, West Virginia, 26506, United States

Location

Universitaetsklinikum Krems

Krems, 3500, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Grand Hopital de Charleroi - Site Saint Joseph

Gilly, 6060, Belgium

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Centre Hospitalier Universitaire Nord

Marseille, 13915, France

Location

Institut Curie

Paris, 75248, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre Hospitalier Universitaire de Rennes - Hopital Pontchaillou

Rennes, 35033, France

Location

Centre Hospitalier Universitaire de Strasbourg - Nouvel Hopital Civil

Strasbourg, 67091, France

Location

Centre Hospitalier Universitaire de Toulouse - Hopital Larrey

Toulouse, 31059, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Koeln

Cologne, 50937, Germany

Location

LungenClinic Grosshansdorf GmbH

Großhansdorf, 22927, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97078, Germany

Location

Henry Dunant Hospital Center

Athens, 11526, Greece

Location

Sotiria General Hospital

Athens, 11527, Greece

Location

Metropolitan Hospital

Athens, 18547, Greece

Location

University Hospital of Heraklion

Heraklion - Crete, 71500, Greece

Location

General Hospital of Patras Agios Andreas

Pátrai, 26335, Greece

Location

Theagenion Cancer Hospital

Thessaloniki, 54007, Greece

Location

Euromedica General Clinic of Thessaloniki

Thessaloniki, 54645, Greece

Location

Agios Loukas Clinic

Thessaloniki, 55236, Greece

Location

Azienda Ospedaliero-Universitaria di Parma

Parma, 43126, Italy

Location

Istituti Fisioterapici Ospitalieri Regina Elena San Gallicano

Rome, 00144, Italy

Location

Azienda Socio Sanitaria Territoriale dei Sette Laghi Ospedale di Circolo e Fondazione Macchi

Varese, 21100, Italy

Location

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Okayama University Hospital

Okayama, Okayama-ken, 700-8558, Japan

Location

Kindai University Hospital

Osakasayama-shi, Osaka, 589-8511, Japan

Location

Shizuoka Cancer Center

Sunto-gun, Shizuoka, 411-8777, Japan

Location

The Cancer Institute Hospital of Japanese Foundation for Cancer Research

Koto-ku, Tokyo, 135-8550, Japan

Location

Wakayama Medical University Hospital

Wakayama, Wakayama, 641-8510, Japan

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Erasmus Medisch Centrum

Rotterdam, 3015 GD, Netherlands

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

Location

Centra Medyczne Medyceusz Sp zoo

Lodz, 91-053, Poland

Location

Mazowieckie centrum leczenia

Otwock, 05-400, Poland

Location

Hospital da Luz, SA

Lisbon, 1500-650, Portugal

Location

Hospital CUF Descobertas

Lisbon, 1998-018, Portugal

Location

Centro Hospitalar Universitario do Porto EPE - Hospital de Santo Antonio

Porto, 4099-001, Portugal

Location

Hospital Cuf porto

Porto, 4100-180, Portugal

Location

Instituto Portugues de Oncologia do Porto Francisco Gentil, EPE

Porto, 4200-072, Portugal

Location

National Cancer Centre Singapore

Singapore, 168583, Singapore

Location

National Cancer Center

Goyang-si Gyeonggi-do, 10408, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Yonsei University Health System Severance Hospital

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung medical center

Seoul, 06351, South Korea

Location

The Catholic University of Korea Seoul St Marys Hospital

Seoul, 06591, South Korea

Location

Hospital Regional Universitario de Malaga

Málaga, Andalusia, 29011, Spain

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Catalonia, 08041, Spain

Location

Instituto Catalan de Oncologia Hospital Duran i Reynals

L'Hospitalet de Llobregat, Catalonia, 08908, Spain

Location

Hospital Universitario Puerta de Hierro Majadahonda

Majadahonda, Madrid, 28222, Spain

Location

Hospital Universitari i Politecnic La Fe

Valencia, Valencia, 46026, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hopitaux Universitaires de Geneve

Geneva, 1211, Switzerland

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Related Publications (7)

• Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 30;389(22):2063-2075. doi: 10.1056/NEJMoa2307980. Epub 2023 Oct 20.

  PMID: 37861218 BACKGROUND

• Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Alvarez JB, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L. Plain language summary: tarlatamab for patients with previously treated small cell lung cancer. Future Oncol. 2024 Dec;20(40):3355-3364. doi: 10.1080/14796694.2024.2402152. Epub 2024 Nov 12.

  PMID: 39530627 BACKGROUND

• Hummel HD, Ahn MJ, Blackhall F, Reck M, Akamatsu H, Ramalingam SS, Borghaei H, Johnson M, Dirnberger F, Cocks K, Huang S, Mukherjee S, Paz-Ares L. Patient-Reported Outcomes for Patients with Previously Treated Small Cell Lung Cancer Receiving Tarlatamab: Results from the DeLLphi-301 Phase 2 Trial. Adv Ther. 2025 Apr;42(4):1950-1964. doi: 10.1007/s12325-025-03136-4. Epub 2025 Mar 3.

  PMID: 40025391 BACKGROUND

• Kong S, Minocha M, Chen PW, Martinez P, Anderson ES, Parkes A, Houk BE, Lin CW. Population Pharmacokinetics of Tarlatamab, a Half-Life Extended DLL3-Directed Bispecific T-Cell Engager in Patients with Previously Treated Small Cell Lung Cancer. Clin Pharmacokinet. 2025 May;64(5):729-741. doi: 10.1007/s40262-025-01499-z. Epub 2025 Apr 22.

  PMID: 40261494 BACKGROUND

• Ahn MJ, Cho BC, Ohashi K, Izumi H, Lee JS, Han JY, Chiang CL, Huang S, Hamidi A, Mukherjee S, Xu KL, Akamatsu H. Asian Subgroup Analysis of Patients in the Phase 2 DeLLphi-301 Study of Tarlatamab for Previously Treated Small Cell Lung Cancer. Oncol Ther. 2025 Dec;13(4):1041-1054. doi: 10.1007/s40487-025-00372-0. Epub 2025 Sep 4.

  PMID: 40908346 BACKGROUND

• Chen PW, Minocha M, Kong S, Jiang T, Anderson ES, Parkes A, Martinez P, Houk BE, Lin CW. Tarlatamab Exposure-Efficacy and Exposure-Safety Relationships to Inform Dose Selection in Patients with Small Cell Lung Cancer. Clin Cancer Res. 2025 Nov 14;31(22):4688-4697. doi: 10.1158/1078-0432.CCR-25-2134.

  PMID: 40928991 BACKGROUND

• Dirnberger F, Wang J, King-Kallimanis B, Cocks K, Skingley G, Clarke N, Huang S, Mukherjee S, Koller M. Derivation of Meaningful Change Thresholds for European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-LC13 in Patients With Small-Cell Lung Cancer. Value Health. 2026 Feb;29(2):223-232. doi: 10.1016/j.jval.2025.09.011. Epub 2025 Sep 25.

  PMID: 41015335 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: September 17, 2021
• First Posted: September 28, 2021
• Study Start: December 1, 2021
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: December 22, 2025

Record last verified: 2025-12

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

DE (3); SG (1); KR (6); ES (8); PT (5); CH (1); TW (2); GB (2); DK (1); AU (2); US (16); NL (2); IT (3); BE (3); GR (8); FR (7); PL (3); JP (7)