A phase 3 study of sacituzumab govitecan in patients with previously treated extensive-stage small cell lung cancer.

Abstract

TPS8137 Background: Treatment options for extensive-stage small cell lung cancer (ES-SCLC) that has progressed after platinum-containing therapy with or without anti–programmed cell death protein (ligand) 1 (anti–PD-[L]1) therapy are limited. Despite the evolving treatment landscape for ES-SCLC, toxicities and poor clinical outcomes with the current globally approved standard of care (SOC), topotecan, highlight the unmet need for novel agents. Sacituzumab govitecan (SG), a Trop-2–directed antibody-drug conjugate, demonstrated encouraging antitumor activity and manageable safety as a second-line treatment for ES-SCLC in the phase 2, open-label TROPiCS-03 study. At a median study follow-up of 12.3 months in TROPiCS-03, the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) was 42% and median overall survival (OS) was 13.6 months. Neutropenia (44%) and diarrhea (9%) were the most common grade ≥3 treatment-emergent adverse events (TEAEs), and no TEAEs led to discontinuation of SG; 1 treatment-related TEAE caused death. EVOKE-SCLC-04 (NCT06801834) is a randomized, phase 3, open-label, multicenter study evaluating the efficacy and safety of SG versus SOC (topotecan, lurbinectedin [in countries/regions where approved], or amrubicin [Japan only]) in patients with previously treated ES-SCLC. Methods: Key eligibility criteria for EVOKE-SCLC-04 include age ≥18 years, confirmed SCLC diagnosis, Eastern Cooperative Oncology Group performance status score of 0–1, measurable disease per RECIST v1.1, and disease progression after 1 prior line of platinum-containing therapy with or without anti–PD-(L)1 therapy. Prior tarlatamab treatment is allowed. Patients with untreated central nervous system (CNS) metastases and/or carcinomatous meningitis are excluded unless these are asymptomatic and immediate CNS-specific treatment is not required. Patients will be randomized 1:1 to either SG (10 mg/kg on Days 1 and 8) or SOC: topotecan (1.5 mg/m 2 daily on Days 1–5), lurbinectedin (3.2 mg/m 2 on Day 1), or amrubicin (40 mg/m 2 daily on Days 1–3) administered as intravenous infusion in 21-day cycles, until progressive disease (assessed by investigator review per RECIST v1.1), unacceptable toxicity, or death. Randomization will be stratified by chemotherapy-free interval (≥90 vs <90 days), CNS involvement (yes vs no), geographic region (East Asia vs non-East Asia), and prior anti–PD-(L)1 therapy (yes vs no). The primary endpoint is OS; secondary endpoints include progression-free survival, ORR, duration of response, patient-reported outcomes (time to first deterioration in shortness of breath and physical functioning), and safety/tolerability. This study is open and actively recruiting as of February 2025 and plans to enroll 695 patients from approximately 275 sites globally. Clinical trial information: NCT06801834 .