Phase 3 Trial of Tarlatamab (SC vs IV) in Extensive-Stage Small Cell Lung Cancer After Platinum Based First-line Chemotherapy (ES-SCLC) (DeLLphi-315)

A Phase 3, Open-Label, Multicenter, Randomized Study of Subcutaneous vs Intravenous Tarlatamab in Participants With Relapsed Extensive-Stage Small Cell Lung Cancer After Platinum-based First-line Chemotherapy (DeLLphi-315)

The primary objective of this study is to demonstrate non-inferiority in pharmacokinetic (PK) parameters of subcutaneous (SC) vs intravenous (IV) tarlatamab administration and to characterize the efficacy, safety, and tolerability of SC tarlatamab in participants with relapsed extensive-stage small-cell lung cancer (ES-SCLC) after platinum-based chemotherapy.

Study Overview

• Status: Recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: Tarlatamab

• Study Type: Interventional
• Enrollment (Estimated): 400
• Phase: Phase 3

Contacts and Locations

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

Study Locations

• Australia
  • South Australia
    • Elizabeth Vale, South Australia, Australia, 5112
      • Recruiting
      • Lyell McEwin Hospital
• China
  • Shanghai, China, 200433
    • Recruiting
    • Shanghai Pulmonary Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
    • Beijing, Beijing Municipality, China, 100020
      • Recruiting
      • Beijing Chaoyang Hospital
• Japan
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8677
      • Recruiting
      • Tokyo Metropolitan Komagome Hospital
• Switzerland
  • Zurich, Switzerland, 8091
    • Recruiting
    • Universitaetsspital Zuerich
• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Recruiting
      • University of Florida Health Cancer Center at Orlando Health
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • Cancer and Hematology Centers of Western Michigan
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Oncology Hematology West PC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 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 ≥ 18 years (or legal adult age within country, whichever is older) at the time of signing the informed consent.
• Histologically or cytologically confirmed SCLC with demonstrated progression or relapse.
• Participants who progressed or recurred following 1 platinum-based regimen.
• Measurable disease as defined per RECIST 1.1 within the 21-day screening period.
• Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1.
• Minimum life expectancy of 12 weeks.
• Adequate organ function.
• History of central nervous system (CNS) metastases are allowed with considerations defined in the protocol.

Exclusion Criteria:

Disease Related

- Any previous diagnosis of non-small cell lung cancer (NSCLC), epidermal growth factor receptor (EGFR) activating mutation that has transformed to SCLC, or mixed SCLC and NSCLC histology, with exceptions defined in the protocol.

Other Medical Conditions

• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 6 months prior to first dose of study treatment.
• History of arterial thrombosis (e.g., stroke or transient ischemic attack) within 6 months prior to first dose of study treatment.
• Current evidence or history of non-infectious pneumonitis/ILD (interstitial lung disease) that required steroids or other immunosuppressive treatment.
• History of other malignancy within the past 2 years, with exceptions defined in the protocol.
• Presence or history of viral infection based on criteria per protocol.
• History of solid organ transplantation.
• Symptoms and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection requiring antibiotics within 7 days prior to the first dose study treatment.
• Known sensitivity or a contraindication to any of the products or components.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures.

Prior/Concomitant Therapy

• Prior systemic anticancer therapy within 30 days of enrolment
• Prior history of severe or life-threatening events from any immune-mediated therapy.
• Receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 14 days prior to first dose of study treatment.
• Live and live-attenuated vaccines within 28 days prior to the start of study treatment.
• Receiving another anticancer therapy for a malignancy other than SCLC.
• More than 1 prior line of anticancer therapy for SCLC.
• Participation in a tarlatamab clinical trial or prior therapy with any selective inhibitor of the delta-like ligand 3 (DLL3) pathway.
• Treatment in an alternative investigational trial within 28 days prior to enrolment.
• History of allergy or hypersensitivity to similar products (eg, drugs with a similar chemical structure or other monoclonal antibody) or any excipient.

Other Exclusions

• Participants unable to have SC injections administered in the abdomen or thigh.
• Participant unlikely to be able to complete all protocol-required procedures, restrictions and requirements.
• History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tarlatamab SC; Participants will receive Tarlatamab via SC injection	Drug: Tarlatamab; Administered via SC injection or IV infusion; Other Names: AMG 757; IMDELLTRA
Active Comparator: Tarlatamab IV; Participants will receive Tarlatamab via IV infusion	Drug: Tarlatamab; Administered via SC injection or IV infusion; Other Names: AMG 757; IMDELLTRA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Curve From Cycle 2 Day 1 to Day 15 (AUC C2D1-D15) of Tarlatamab	From Cycle 2 Day 1 to Day 15 (each cycle is 28 days)
Predose Concentration (Ctrough) of Tarlatamab	On Cycle 2 Day 15 (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Up to approximately 4 years
Responses to Patient-Reported Adverse Events Questionnaire (PRO-CTCAE)	Up to approximately 4 years
Objective response (OR) per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)	Up to approximately 4 years
Progression free survival (PFS) per RECIST v1.1	Up to approximately 4 years
Duration of response (DOR) per RECIST v1.1	Up to approximately 4 years
Disease control (DC) per RECIST v1.1	Up to approximately 4 years
Number of participants with treatment-emergent adverse events (TEAEs) and Treatment-related Adverse Events (TRAEs)	Up to approximately 4 years
Change from Baseline in Visual Analogue Scale (VAS) score of the EuroQol5 Dimension (EQ-5D-5L)	Up to approximately 4 years
Responses to Functional Assessment of Cancer Therapy - General (FACT-G) questionnaire on symptom bother	Up to approximately 4 years
Responses to Therapy Administration Satisfaction Questionnaire (TASQ)	Up to approximately 4 years
Number of Participants with Anti-tarlatamab Antibody Formation	Up to approximately 4 years

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 28, 2026
• Primary Completion (Estimated): September 24, 2027
• Study Completion (Estimated): July 30, 2030

Study Registration Dates

• First Submitted: August 12, 2026
• First Submitted That Met QC Criteria: August 20, 2026
• First Posted (Actual): August 21, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 16, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: ES-SCLC; Tarlatamab
• 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; AMG 757
• Other Study ID Numbers: 20250046

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