The PESGA Trial: A Prospective, Open-Label, Single-Arm, Phase II Study to Evaluate First Line Therapy for Extensive-Stage Small Cell Lung Cancer (ES-SCLC) Patients, Treated by Induction Carboplatin/Etoposide/Pembrolizumab Followed by Maintenance of Pembrolizumab/ Sacituzumab Govitecan

Introduction: Despite recent advances in immunotherapy combinations for extensive-stage small cell lung cancer (ES-SCLC), rapid disease progression following chemotherapy discontinuation remains a significant challenge. While the addition of pembrolizumab to platinum-etoposide has demonstrated a modest improvement in progression-free survival (PFS), there is an urgent need for more effective maintenance strategies. Sacituzumab govitecan (SG), an antibody-drug conjugate targeting Trop-2, has shown promising activity in pretreated ES-SCLC. This phase II study evaluates the efficacy and safety of adding SG to pembrolizumab maintenance therapy following chemoimmunotherapy induction in treatment-na & iuml;ve ES-SCLC patients. Methods: In the PESGA trial, a prospective, open-label, single-arm phase II trial, patients with previously untreated ES-SCLC will receive induction therapy consisting of pembrolizumab (200 mg Q3 W) plus carboplatin (AUC 5) and etoposide (100 mg/m(2) Days 1-3) for 4 cycles. This will be followed by maintenance therapy combining pembrolizumab (200 mg Q3 W) with SG (10 mg/kg on Days 1 and 8 of 21-day cycles) for up to 31 cycles. The primary endpoint is PFS from the start of induction treatment. Secondary endpoints include overall survival, duration of response, and safety. Exploratory analyses will investigate molecular resistance mechanisms through sequential liquid and tissue biopsies and evaluate correlations between tumor Trop-2 expression and clinical outcomes. The study plans to enroll 21 patients over 18 months, with an estimated total study duration of 54 months. Results will be analyzed after 50% of patients have achieved PFS. Conclusions: The PESGA study design builds upon the KEYNOTE-604 regimen by incorporating SG into the maintenance phase, potentially addressing the challenge of early progression in ES-SCLC. The study may provide valuable insights into novel maintenance strategies and molecular mechanisms of treatment resistance in ES-SCLC.