A Randomized, Open-label, Phase 3 Study of Tarlatamab Compared With Standard of Care in Subjects With Relapsed Small Cell Lung Cancer After Platinum-based First-line Chemotherapy (DeLLphi-304)

The primary objective of this study is to evaluate the efficacy of tarlatamab compared to the standard of care in prolonging overall survival in subjects with relapsed small cell lung cancer following platinum-based first-line chemotherapy. Secondary objectives include the assessment of progression-free survival according to RECIST 1.1 criteria and the evaluation of patient-reported outcomes, specifically disease-related symptoms, physical function, and quality of life.

This study involves a total of 326 patients diagnosed with small cell lung cancer. The study population includes both male and female participants within specific age categories. Inclusion requires histological or cytological confirmation of relapsed/refractory disease following at least one platinum-based regimen. Eligible individuals must demonstrate measurable disease according to RECIST 1.1 and possess an Eastern Cooperative Oncology Group performance status of 0 or 1. Additional requirements include a minimum life expectancy of 12 weeks and adequate organ function.

This Phase 3, randomized, open-label study is designed to compare the efficacy of tarlatamab against standard of care in subjects with relapsed small cell lung cancer following platinum-based chemotherapy. The primary endpoint is overall survival, defined as the time from the initiation of treatment until death from any cause. Secondary endpoints include the duration until disease progression or death and changes from baseline in patient-reported outcomes, such as chest pain, cough, chest tightening, physical function, and global health status. The trial utilizes topotecan as a comparator, with dexamethasone, siltuximab, tocilizumab, and electrolytes serving as auxiliary treatments. Eligible participants must have histologically or cytologically confirmed relapsed or refractory disease, a measurable disease per RECIST 1.1 within the screening period, an ECOG performance status of 0 or 1, and adequate organ function. The study is expected to be active through March 2028.

Tarlatamab is administered as a powder for solution for infusion via intravenous injection at a dose of 10 mg.

Topotecan is utilized as a comparator treatment and is administered either orally at a dose of 2.3 mg/m2 or through intravenous use at a dose of 1.5 mg/m2.

Dexamethasone is provided as background therapy via intravenous use at a dose of 8 mg.

Siltuximab is administered as background therapy via intravenous use at a dose of 11 mg/kg.

Tocilizumab is administered as auxiliary therapy via IV infusion at a dose of 32 mg/kg.

Electrolytes are administered via intravenous route at a volume of 1 litre.

The primary efficacy endpoint for this study is overall survival, which is defined as the duration from the initiation of treatment with either tarlatamab or standard of care until death from any cause in subjects with small cell lung cancer.

Secondary efficacy assessments include:

• The time from randomization to disease progression or death.
• Changes from baseline in patient-reported outcomes, which are evaluated every 6 weeks up to 18 weeks. These assessments utilize the EORTC-QLQ-LC13 and EORTC-QLQ-C30 instruments to measure symptoms such as chest pain, cough, and tightening in the chest, as well as physical function and global health status.