Phase 3 Randomized Study of Tarlatamab Versus Placebo in Limited-Stage Small-Cell Lung Cancer Post-Concurrent Chemoradiation Therapy

The primary objective is to compare the efficacy of tarlatamab with placebo in subjects with limited-stage small-cell lung cancer who have not progressed following concurrent chemoradiation therapy, as assessed by progression-free survival (PFS) using blinded independent central review (BICR) per RECIST 1.1. Additionally, the study aims to compare efficacy regarding overall survival (OS).

Secondary objectives include:

• Evaluation of efficacy through PFS and time to progression (TTP) based on both investigator assessment and BICR, including specific time points at 6 months, 1 year, and 2 years.
• Assessment of OS at intervals of 6 months, 1 year, 2 years, and 3 years from randomization.
• Description of efficacy through complete response (CR) and its duration.
• Characterization of pharmacokinetics (PK) and evaluation of immunogenicity.
• Examination of safety and tolerability.

This clinical trial involves 255 participants diagnosed with limited-stage small-cell lung cancer. The study population includes both male and female individuals within specific age categories. Eligible participants must have histologically or cytologically confirmed small-cell lung cancer and must have undergone treatment consisting of concurrent chemotherapy and radiotherapy. Selection is contingent upon the completion of chemoradiotherapy without disease progression as defined by RECIST 1.1. Participants are required to have an Eastern Cooperative Oncology Group performance status of 0 or 1, a minimum life expectancy of 12 weeks, and adequate organ function. Additionally, any toxicities resulting from concurrent chemoradiotherapy, excluding alopecia or fatigue, must have resolved to a grade of 1 or less.

This Phase 3, randomized, double-blind, placebo-controlled, multicenter study is designed to evaluate the efficacy of tarlatamab compared to a placebo in subjects diagnosed with limited-stage small-cell lung cancer. The primary objectives are to assess progression-free survival via blinded independent central review and overall survival. Secondary endpoints include investigator-assessed progression-free survival, complete response rates, time to progression, and the incidence of treatment-emergent adverse events. The study involves a screening process to confirm histological diagnosis, completion of chemoradiotherapy without disease progression, and adequate organ function. The estimated trial duration extends from November 2024 to May 2030.

Tarlatamab is an experimental therapeutic administered via intravenous use. The medication is provided as a powder for solution for infusion or as a solution for injection/infusion.

A placebo for tarlatamab is utilized as a comparator in the study.

Background and auxiliary treatments include tocilizumab administered through intravenous routes, siltuximab via intravenous use, and dexamethasone by intravenous use. Betamethasone sodium phosphate, provided as prednisolone, is administered via oral use. Buclizine hydrochloride, paracetamol, and codeine phosphate are administered orally. Mannitol is utilized as an electrolyte through intravenous use, while argipressin is administered via oral use.

The efficacy of tarlatamab will be evaluated using several primary and secondary endpoints. The primary assessment of efficacy is based on progression-free survival (PFS), which is determined via blinded independent central review (BICR) according to RECIST 1.1 criteria. Additionally, overall survival (OS) is utilized as a primary endpoint to compare the efficacy of tarlatamab against placebo.

Secondary efficacy parameters include:

• PFS as assessed by investigator evaluation.
• Complete response (CR) based on both BICR and investigator assessment per RECIST 1.1.
• Duration of complete response.
• PFS and OS rates at 6 months, 1 year, and 2 years following randomization.
• OS rates at 6 months, 1 year, 2 years, and 3 years from randomization.
• Time to progression (TTP).
• Serum concentration of tarlatamab.
• Incidence of anti-tarlatamab antibody formation.
• Incidence of treatment-emergent adverse events following randomization.