Abstract 342TiP
Background
Small cell lung cancer (SCLC) accounts for approximately 15% of lung cancers, characterized by aggressive growth and early metastasis. Most patients present with extensive-stage disease (ESSCLC), resulting in poor prognosis and limited survival. The KEYNOTE-604 trial demonstrated that adding pembrolizumab, an anti-PD-1 inhibitor, to standard platinum-etoposide chemotherapy has slightly improved progression-free survival 4.5 [4.3–5.4] mo) compared to chemotherapy alone (4.3 [4.2–4.4] mo; hazard ratio [HR]=0.75 [95% CI: 0.61–0.91], p=0.0023). However, rapid disease progression often occurs after chemotherapy discontinuation, highlighting the need for effective maintenance strategies. Sacituzumab govitecan (SG), an antibody-drug conjugate targeting Trop-2, has shown encouraging results in pretreated ES-SCLC patients, with a 41.9% overall response rate, median duration of response of 4.7 months, median PFS of 4.4 months, and median OS of 13.6 months. This study based on the KEYNOTE-604 treatment algorithm, aims to evaluate the efficacy and safety of adding SG to pembrolizumab during the maintenance phase for previously untreated ES-SCLC patients.
Trial design
The PESGA trial is a prospective, open-label, single-arm, phase II study evaluating a novel first-line therapy approach for ES-SCLC. Patients will receive induction therapy with pembrolizumab (200 mg Q3W) plus etoposide-platinum for 4 cycles, followed by maintenance therapy combining pembrolizumab with SG (10 mg/kg on Days 1 and 8 of 21-day cycles) for up to 31 cycles. The primary endpoint is progression-free survival (PFS), measured from induction initiation to disease progression or death. Secondary endpoints include overall survival, duration of response, and safety assessments. Exploratory objectives aim to elucidate molecular resistance profiles through liquid and tissue biopsies and investigate correlations between tumour Trop-2 expression levels and efficacy outcomes.
Clinical trial identification
NCT06667167, SZMC-0079-24.
Legal entity responsible for the study
Shaare Zedek Medical Center.
Funding
Investigator Initiated Study supported by Merck Sharp and Dohme (MSD), and Gilead Sciences, Inc.
Disclosure
N. Peled: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Foundation Medicine, Gaurdant360, Merk, MSD, Novartis, NovellusDx, Pfizer, Roche, and Takeda. All other authors have declared no conflicts of interest.