Phase 2 Study of ABBV-706 and Atezolizumab versus Standard of Care in Patients with Previously Untreated Extensive-Stage Small Cell Lung Cancer

The primary objectives of this study are to evaluate the safety and tolerability of ABBV-706 in combination with atezolizumab, to determine the recommended Phase 3 dose, and to assess efficacy via progression-free survival in patients with previously untreated extensive stage small cell lung cancer. Secondary objectives include:

• Further assessment of efficacy through overall response rate, duration of response, disease control rate, and overall survival.
• Characterization of pharmacokinetics and immunogenicity of the combination therapy.

This clinical trial involves 120 patients diagnosed with extensive stage small cell lung cancer. The study population includes both male and female individuals within the age range of 40 to 60 years. Participants must have a histologically or cytologically confirmed diagnosis requiring first line therapy. Eligible subjects are required to have an Eastern Cooperative Oncology Group Performance Status of 0 or 1. Inclusion necessitates that participants are suitable for a regimen consisting of atezolizumab and platinum-based chemotherapy, specifically involving carboplatin and etoposide. Furthermore, subjects must present with measurable disease according to the Response Evaluation Criteria in Solid Tumors. The objectives are:

• To evaluate the safety and tolerability of ABBV-706 in combination with atezolizumab
• To optimize and select the recommended Phase 3 dose of ABBV-706 in combination with atezolizumab
• To evaluate efficacy as measured by progression-free survival

This Phase 2, randomized, open-label, multicenter study is designed to evaluate the safety, tolerability, and efficacy of ABBV-706 in combination with atezolizumab compared to the standard of care in subjects with previously untreated extensive stage small cell lung cancer. The primary efficacy endpoint is progression-free survival as assessed by the investigator using RECIST v1.1. Secondary endpoints include overall response rate, duration of response, disease control, and overall survival. The research methodology aims to optimize and select the recommended Phase 3 dose of the investigational combination. The study involves a screening period to confirm histological diagnosis, ECOG performance status, and measurable disease, followed by intravenous administration of the assigned treatment regimens. The trial is expected to occur between March 2026 and May 2029.

ABBV-706 is an experimental humanised IgG1 monoclonal antibody against SEZ6, conjugated to (2S)-2-(2-bromoacetamido)-N-[(2S)-1-({3-[(7S)-7-ethyl-7-hydroxy-8,11-dioxo-7,8,11,13-tetrahydro-2H,10H-[1,3]dioxolo[4,5-g]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-14-yl]bicyclo[1.1.1]pentan-1-yl}amino)-1-oxopropan-2-yl]-3-methylbutanamide. The medicinal product is administered as a solution for infusion via an intravenous route.

Atezolizumab is utilized as a comparator treatment administered through intravenous infusion.

Carboplatin is utilized as a comparator treatment administered through intravenous infusion.

Etoposide is utilized as a comparator treatment administered through intravenous infusion.

The efficacy of ABBV-706 in combination with atezolizumab for the treatment of extensive stage small cell lung cancer is evaluated using several clinical endpoints. The primary endpoint is progression-free survival (PFS), which is determined via investigator assessment according to RECIST v1.1.

Secondary efficacy parameters include:

• Overall response rate (ORR)
• Duration of response (DoR)
• Disease control (DC)
• Overall survival (OS)