EVOKE-01: A phase 3 study of sacituzumab govitecan (SG) versus docetaxel in patients with non–small cell lung cancer (NSCLC) progressing on or after platinum-based chemotherapy and checkpoint inhibitors.
Marina Chiara Garassino, Douglas Reznick, Steven Y. Liu, Niels Reinmuth, Nicolas Girard, Filippo de Marinis, Sabeen Mekan, Riddhi Patel, Michelle Ding, Luis Paz‐Ares
Abstract
TPS9149 Background: Single-agent chemotherapy, such as docetaxel, is the standard of care in patients with metastatic NSCLC who progressed on platinum-based therapy and checkpoint inhibitors. However, docetaxel is associated with poor survival (median overall survival [OS] of < 1 year); thus, novel agents are needed to further improve outcomes in this setting. SG is an antibody-drug conjugate composed of an anti–Trop-2 antibody coupled to the cytotoxic SN-38 payload via a proprietary, hydrolyzable linker. In a single-arm expansion of the phase 1/2 IMMU-132-01 basket study of advanced epithelial cancers (NCT01631552), SG demonstrated an objective response rate (ORR) of 17% and median OS of 9.5 months, with a manageable safety profile in 54 patients with metastatic NSCLC who had multiple prior therapies (Heist RS, et al. J Clin Oncol. 2017). EVOKE-01 randomized phase 3 study was designed to further evaluate SG in patients with metastatic NSCLC. Methods: EVOKE-01 (NCT05089734) is an open-label, global, multicenter, randomized, phase 3 study comparing the efficacy and safety of SG vs docetaxel in patients with metastatic NSCLC. Key eligibility criteria include age ≥18 years, pathologically documented stage IV NSCLC at time of study entry, and progression after platinum-based chemotherapy and anti-PD(L)1 therapy given either in combination or sequentially. Patients with EGFR, ALK, or other known actionable genomic alterations must have also received treatment with ≥1 approved appropriate TKI. Other inclusion criteria are ECOG performance status 0-1 and adequate hematologic, hepatic, and renal function. Patients with prior treatment with topoisomerase inhibitors are excluded. Patients are randomized 1:1 to receive intravenous SG (10 mg/kg on day 1 and 8) or docetaxel (75 mg/m 2 on day 1) in 21-day cycles until progressive disease or unacceptable toxicity. Stratification is based on predominant histology (squamous vs nonsquamous), best response to prior immune therapy (PD/SD vs CR/PR), and prior therapy for actionable genomic alteration (yes vs no). The primary endpoint is OS. Key secondary endpoints include progression-free survival, ORR, duration of response, and disease control rate, as assessed by investigator RECIST v1.1, mean change from baseline in NSCLC-SAQ total score and shortness of breath, and safety. This study plans to enroll ̃520 patients globally and is open for recruitment. Clinical trial information: NCT05089734.