SEZanne: A phase 2 randomized, open-label, multicenter study to evaluate the optimal dose, safety, and efficacy of ABBV-706 in combination with atezolizumab (atezo) versus standard of care (SOC) in patients (pts) with previously untreated extensive-stage (ES) small cell lung cancer (SCLC)

Abstract

SEZanne: A phase 2 randomized, open-label, multicenter study to evaluate the optimal dose, safety, and efficacy of ABBV-706 in combination with atezolizumab (atezo) versus standard of care (SOC) in patients (pts) with previously untreated extensive-stage (ES) small cell lung cancer (SCLC). Background: SCLC is a neuroendocrine tumor accounting for ~15% of lung cancers, with a 5-year survival rate of ~7%. Platinum-based chemotherapy (PCT) remains the 1L SOC, achieving response rates of 60-70% in pts with ES-SCLC, though durable responses are rare. Adding a PD-L1 inhibitor (atezo or durvalumab) to PCT only modestly improves survival, and novel therapies are needed. Seizure-related homolog 6 (SEZ6), a neuroendocrine lineage marker highly expressed in SCLC, represents a promising target. ABBV-706, a SEZ6-directed antibody-drug conjugate with a topoisomerase 1 inhibitor payload, has shown promise as monotherapy in pts with relapsed SCLC, with an ORR of 57.3% (Byers et al. J Thorac Oncol. 2025;10:S23). The phase 2 SEZanne study (NCT07155174) evaluates the dose optimization, safety, and efficacy of ABBV-706 + atezo as a 1L regimen vs SOC. Methods: This global, open-label, randomized phase 2 study (~75 sites; up to 180 pts) compares ABBV-706 + atezo vs SOC. Eligible pts ($18 years) have ES-SCLC requiring 1L therapy, ECOG 0-1, measurable disease per RECIST v1.1, and are candidates for PCT. Primary objectives are to evaluate safety/tolerability, identify the recommended phase 3 dose, and assess PFS of ABBV-706 in combination with atezo. Secondary objectives are to further evaluate efficacy (ORR, DOR, DCR, OS) and characterize the PK/ immunogenicity of the combination. The study consists of 2 parts: a safety lead-in (~30 pts) and a dose optimization (~150 pts) stage. During safety lead-in, pts are randomized 1:1: 1 to 2 doses of ABBV-706 Q3W + atezo or SOC. SOC includes 4 cycles of PCT (carboplatin) + etoposide + atezo followed by atezo maintenance; lurbinectedin may also be used in maintenance where locally approved. After the safety lead-in, additional pts will be randomized to the ABBV-706 + atezo arms that were deemed safe, or the SOC arm. Treatment continues until progression, intolerable toxicity, or other discontinuation criteria are met. The study is enrolling. Clinical trial information: NCT07155174. Research Sponsor: AbbVie Inc.