NCT07423585

Tarlatamab for the Treatment of Extensive Stage Small-cell Lung Cancer

A Front-Line Window-of-Opportunity Phase 2 Study of Tarlatamab (Bispecific T Cell Engager: DLL3-CD3) in Patients With Extensive-Stage Small-Cell Lung Cancer

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Sponsor: Asrar Alahmadi · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests the effect of tarlatamab in treating patients with small cell lung cancer (SCLC) that has spread from where it first started to other parts of the body (extensive-stage). SCLC is an aggressive cancer which has a low 5-year survival rate. Tarlatamab is a bispecific antibody that can bind to two different antigens at the same time. Tarlatamab binds to DLL3 which is a protein found on the surface of some types of tumor cells, including small-cell lung cancer, and to CD3 which is present on immune system T-cells (a type of white blood cell) and may interfere with the ability of tumor cells to grow and spread. This may increase the length of time to progression (growing, spreading, or getting worse) and help patients with extensive-stage SCLC live longer.

Detailed description

PRIMARY OBJECTIVES: I. To assess the 6-month progression-free survival (PFS) rate for extensive-stage SCLC (ES-SCLC) patients treated with tarlatamab as first-line therapy. II. Interim analysis for futility monitoring: To monitor rate of rapid disease progression (PD) at 4 weeks, with a goal of \< 40%. SECONDARY OBJECTIVES: I. To evaluate the safety and toxicity of tarlatamab as first-line therapy ES-SCLC using National Cancer Institute (NCI) Common Terminology Criteria (CTCAE) version 5.0 for all adverse events (AEs) and the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading Criteria for cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). II. To assess objective response rate (ORR), duration of response (DOR), and disease control rate (DCR) in ES-SCLC patients treated with tarlatamab in first-line settings as measured by Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. III. To evaluate the intracranial (ic) antitumor activity of tarlatamab as first-line therapy in ES-SCLC with baseline brain metastasis as measured by ic best ORR, time to intracranial response, icDOR, and icPFS rate at 6 months. IV. To assess median PFS, 12-month overall survival (OS), and median OS in ES-SCLC patients treated with tarlatamab in first-line settings. EXPLORATORY OBJECTIVES: I. To assess quality of life (QoL) as measured by the Functional Assessment of Cancer Therapy-Lung (FACT-L) QOL. II. To assess the clinical efficacy of platinum-based chemotherapy (PC) and immune checkpoint inhibitors (ICI) in second-line settings (progression on tarlatamab) as measured by time to second progression (PFS2). III. To measure the time to initiation of PC and ICI in ES-SCLC (after disease progression on tarlatamab). OUTLINE: Patients receive tarlatamab intravenously (IV) over 60 minutes on days 1, 8, and 15 of cycle 1, then on days 1 and 15 of remaining cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients receive saftey response assessment scan after 4 weeks of starting treatment. Pateints with rapid disease progression will immediatly start standard of care platinum based chemotherapy and immune checkpoint inhibitors. Response assessment scans will be done every 8 weeks (2 cycles). After completion of study treatment, patients are followed at 30 days then every 3 months for up to 2 years.

Conditions

• Extensive Stage Lung Small Cell Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo biopsies
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo computed tomography
PROCEDURE	Echocardiography Test	Undergo ECHO
OTHER	Electronic Health Record Review	Ancillary studies
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
PROCEDURE	Multigated Acquisition Scan	Undergo MUGA
OTHER	Questionnaire Administration	Ancillary studies
DRUG	Tarlatamab	Given IV

Timeline

• Start date: 2026-04-01
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2026-02-20
• Last updated: 2026-02-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study