Tarlatamab plus Durvalumab versus Durvalumab Alone in Patients with Extensive-Stage Small Cell Lung Cancer Following Platinum-Etoposide Therapy

The primary objective of this study is to compare the efficacy of tarlatamab plus durvalumab versus durvalumab alone in prolonging overall survival in subjects with extensive stage small cell lung cancer. Secondary objectives include:

• Evaluation of progression-free survival as assessed by investigator assessment per RECIST 1.1.
• Comparison of objective response, disease control, and duration of response.
• Assessment of progression-free survival at 6 months, 1 year, and 2 years, overall survival at 6 months, 1 year, 2 years, and 3 years, and time to progression.
• Comparison of safety and tolerability.
• Characterization of pharmacokinetics of tarlatamab in combination with durvalumab.
• Evaluation of immunogenicity of tarlatamab.
• Comparison of treatment effects on disease symptoms, physical function, and quality of life.

This clinical trial involves 240 participants diagnosed with extensive stage small cell lung cancer. The study population includes both male and female patients within specific age ranges. Eligible subjects must have an Eastern Cooperative Oncology Group performance status of 0 or 1 and a minimum life expectancy exceeding 12 weeks. Participants are required to have completed 4 cycles of platinum-etoposide chemotherapy with concurrent durvalumab as first-line treatment without disease progression, as determined by RECIST 1.1. Inclusion necessitates adequate organ function and the resolution of toxicities from concurrent chemoradiotherapy to a grade of ≤ 1, excluding alopecia or fatigue.

This Phase 3, open-label, multicenter, randomized study is designed to evaluate the efficacy of tarlatamab in combination with durvalumab compared to durvalumab monotherapy for the treatment of extensive stage small cell lung cancer. The primary objective is to compare overall survival between the two treatment arms. Secondary endpoints include progression-free survival, time to progression, and the incidence of treatment-emergent adverse events. The study is expected to involve recruitment and follow-up through September 2028. Eligible subjects must be at least 18 years of age, have an ECOG performance status of 0 or 1, and have completed four cycles of platinum-etoposide chemotherapy with concurrent durvalumab without disease progression. Participation involves an initial screening process to confirm eligibility based on organ function and life expectancy, followed by treatment and subsequent monitoring to assess efficacy and safety.

Tarlatamab is an investigational orphan drug administered as a powder for solution for infusion via intravenous use at a dose of 00 mg.

Durvalumab is a test therapeutic administered via intravenous use at a dose of 9999.

Carboplatin is used as an auxiliary treatment via intravenous use at a dose of 9999.

Cisplatin is used as an auxiliary treatment via intravenous use at a dose of 9999.

Dexamethasone is used as an auxiliary treatment via intravenous use at a dose of 8 mg.

Etoposide is used as an auxiliary treatment via intravenous use at a dose of 9999.

Infliximab is used as an auxiliary treatment via intravenous use at a dose of 9999.

Mannitol, classified as electrolytes, is administered via intravenous use at a dose of 1 litre(s).

Mycophenolate mofetil is used as an auxiliary treatment via oral use at a dose of 9999.

Paracetamol, which contains buclizine hydrochloride and codeine phosphate, is used as an auxiliary treatment via oral use at a dose of 9999.

Prednisolone, containing betamethasone sodium phosphate, is used as an auxiliary treatment via oral use at a dose of 1 mg/kg.

Siltuximab is used as an auxiliary treatment via intravenous use at a dose of 11 mg/kg.

Tocilizumab is used as an auxiliary treatment via intravenous use at a dose of 8 mg/kg.

Vasopressin, also known as argipressin, is used as an auxiliary treatment via oral use at a dose of 9999.

The primary efficacy endpoint for this study is overall survival. Secondary endpoints include progression-free survival, time to progression, objective response, duration of response, and disease control. Assessment of progression-free survival rates will occur at 6 months, 1 year, and 2 years following randomization. Additionally, overall survival rates will be evaluated at 6 months, 1 year, 2 years, and 3 years from randomization. The time to first deterioration will be measured in relation to physical function and global health status or quality of life.

Clinical efficacy will also be evaluated through the following parameters:

• Changes from baseline in disease symptoms, specifically cough, chest pain, and dyspnea, measured up to week 13 and week 25.
• Serum concentrations of tarlatamab.
• Incidence of anti-tarlatamab antibody formation.
• Incidence of treatment-emergent adverse events.