Study of Tarlatamab in Combination With YL201 With or Without Anti-programmed Death Ligand 1 (PD-L1) in Participants With Extensive Stage (ES) Small Cell Lung Cancer (SCLC) ((DeLLphi-310))

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Tarlatamab in Combination With YL201 With or Without Anti-PD-L1 in Subjects With Extensive Stage Small Cell Lung Cancer

The primary objective of this study is to evaluate the safety and tolerability of tarlatamab in combination with YL201 with or without anti-PD-L1.

Study Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Tarlatamab; Drug: YL201; Drug: Durvalumab

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Québec, Quebec, Canada, G1J 1Z4
      • CHU de Quebec Hopital de l Enfant Jesus
• China
  • Fuzhou, China, 350011
    • Fujian Cancer Hospital
  • Shandong
    • Jinan, Shandong, China, 250117
      • Shandong Cancer Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 611135
      • West China Hospital of Sichuan University
• France
  • Bordeaux, France, 33000
    • Institut Bergonie
  • Lyon, France, 69373
    • Centre Léon Bérard
  • Toulouse, France, 31059
    • Institut Universitaire du Cancer Toulouse Oncopole
  • Villejuif, France, 94805
    • Gustave Roussy
• Germany
  • Essen, Germany, 45147
    • Universitaetsklinikum Essen
• Greece
  • Athens, Greece, 11528
    • Alexandra Hospital
  • Athens, Greece, 11526
    • Henry Dunant Hospital Center
  • Thessaloniki, Greece, 57001
    • European Interbalkan Medical Center
  • Thessaloniki, Greece, 57001
    • Iatriko Diavalkaniko Thessalonikis
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem
  • Gyöngyös, Hungary, 3200
    • Clinexpert Kft Bugat Pal Korhaz
• Italy
  • Candiolo to, Italy, 10060
    • Istituto di Candiolo Fondazione del Piemonte per l Oncologia IRCCS
  • Meldola (FC), Italy, 47014
    • Istituto Romagnolo per lo Studio dei Tumori Dino Amadori
  • Milan, Italy, 20162
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
  • Seoul, South Korea, 03722
    • Severance Hospital Yonsei University Health System
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Catalonia
    • Barcelona, Catalonia, Spain, 08041
      • Hospital de la Santa Creu i Sant Pau
    • Barcelona, Catalonia, Spain, 08035
      • Hospital Universitari Vall D Hebron
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro Majadahonda
• United States
  • California
    • Irvine, California, United States, 92618
      • City of Hope Orange County Lennar Foundation Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Siteman Cancer Center
  • North Dakota
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
  • South Dakota
    • Sioux Falls, South Dakota, United States, 54104
      • Sanford Oncology Clinic and Pharmacy
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Medical Center
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants ≥ 18 years of age (or legal adult age within country) at time of signing informed consent.
• Participants with histologically or cytologically confirmed ES-SCLC.
• For Parts 1 and 2, subjects must have ES-SCLC that has progressed or recurred following at least 1 prior line of platinum-based anti-cancer therapy received either for LS-SCLC or ES-SCLC.
• For Part 3, subjects must have ES-SCLC and no prior systemic treatment for ES SCLC other than 1 cycle of platinum-based chemotherapy, and etoposide, and with or without PD-(L)1 inhibitor in the first-line setting.
• At least 1 measurable lesion as defined by RECIST 1.1.
• Participants must have adequate organ function (cardiac, pulmonary, kidney, bone marrow, and liver).

Exclusion Criteria:

• Prior delta-like ligand 3 (DLL3) or B7 homolog 3 (B7-H3) targeted therapy.
• Prior exposure to topoisomerase I inhibitors or antibody-drug conjugate (ADC) with topoisomerase I inhibitor payload.
• Symptomatic central nervous system (CNS) metastases. Note: Participants with asymptomatic brain metastases are eligible as defined in the protocol.
• History of (non-infectious) interstitial lung disease (ILD)/pneumonitis that required corticosteroids, current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Baseline requirement of supplemental oxygen.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Exploration (Part 1); Multiple dose levels of YL201 will be explored in combination with tarlatamab administered intravenously (IV) at a fixed dose using one-step dosing.	Drug: Tarlatamab; Tarlatamab will be administered as an IV infusion.; Drug: YL201; YL201 will be administered as an IV infusion.
Experimental: Dose Expansion (Part 2); YL201 will be administered at the selected maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) in combination with tarlatamab administered IV at a fixed dose.	Drug: Tarlatamab; Tarlatamab will be administered as an IV infusion.; Drug: YL201; YL201 will be administered as an IV infusion.
Experimental: Triplet Combination (Part 3); YL201 will be administered at MTCD or RP2D in combination with tarlatamab and an anti-PD-L1 (durvalumab) administered IV at a fixed dose.	Drug: Tarlatamab; Tarlatamab will be administered as an IV infusion.; Drug: YL201; YL201 will be administered as an IV infusion.; Drug: Durvalumab; Durvalumab will be administered as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants Experiencing Dose-limiting toxicities (DLTs)	Up to Day 21
Number of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)	Up to 3.5 Years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	Up to 3.5 Years
Duration of Response (DOR) per RECIST 1.1	Up to 3.5 Years
Time to Response (TTR) per RECIST 1.1	Up to 3.5 Years
Disease Control Rate (DCR) per RECIST 1.1	Up to 3.5 Years
Progression-free Survival (PFS) per RECIST 1.1	Up to 3.5 Years
Time to Progression (TTP) per RECIST 1.1	Up to 3.5 Years
Time to Subsequent Therapy	Up to 3.5 Years
Overall Survival (OS)	Up to 3.5 Years
Maximum Serum Concentration (Cmax) of Tarlatamab	Up to Week 36
Minimum Serum Concentration (Cmin) of Tarlatamab	Up to Week 36
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval for Tarlatamab	Up to Week 36
Half-life (t1/2) of Tarlatamab	Up to Week 36

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2025
• Primary Completion (Estimated): June 23, 2031
• Study Completion (Estimated): June 23, 2031

Study Registration Dates

• First Submitted: March 21, 2025
• First Submitted That Met QC Criteria: March 21, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 20, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Anti-PD-L1; Small cell lung cancer; Durvalumab; SCLC; Tarlatamab; YL201
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; durvalumab
• Other Study ID Numbers: 20240124 (JohannesGU)

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 .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