Sacituzumab Govitecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non-Small Cell Lung Cancer: The Randomized, Open-Label Phase III EVOKE-01 Study

Abstract

Purpose: The open-label, phase III EVOKE-01 study evaluated sacituzumab govitecan (SG) versus standard-of-care docetaxel in metastatic non-small cell lung cancer (mNSCLC) with progression on/after platinum-based chemotherapy, anti-PD-(L)1, and targeted treatment for actionable genomic alterations (AGAs). Primary analysis is reported.

Methods: Patients were randomly assigned 1:1 (stratified by histology, best response to last anti-PD-(L)1-containing regimen, and AGA treatment received or not) to SG (one 10 mg/kg intravenous infusion on days 1 and 8) or docetaxel (one 75 mg/m² intravenous infusion on day 1) in 21-day cycles. Primary end point was overall survival (OS). Key secondary end points were investigator-assessed progression-free survival (PFS), objective response rate, patient-reported symptom assessment, and safety.

Results: In the intention-to-treat population (SG, n = 299; docetaxel, n = 304), 55.4% had one previous line of therapy. Median follow-up was 12.7 months (range, 6.0-24.0). The primary end point was not met. There was a numerical OS improvement for SG versus docetaxel (median, 11.1 v 9.8 months; hazard ratio [HR], 0.84 [95% CI, 0.68 to 1.04]; one-sided P = .0534), consistent across squamous and nonsquamous histologies. Median PFS was 4.1 versus 3.9 months (HR, 0.92 [95% CI, 0.77 to 1.11]). An OS benefit was observed for SG (n = 192) versus docetaxel (n = 191) in mNSCLC nonresponsive to last anti-PD-(L)1-containing regimen (3.5-month median OS increase; HR, 0.75 [95% CI, 0.58 to 0.97]); this was consistent across histologies. Among patients receiving SG and docetaxel, 6.8% and 14.2% discontinued because of treatment-related adverse events (TRAEs), respectively; 1.4% and 1.0%, respectively, had TRAEs leading to death.

Conclusion: Although statistical significance was not met, OS numerically improved with SG versus docetaxel, which was consistent across histologies. Clinically meaningful improvement in OS was noted in mNSCLC nonresponsive to last anti-PD-(L)1-containing regimen. SG was better tolerated than docetaxel and consistent with its known safety profile, with no new safety signals.

Trial registration: ClinicalTrials.gov NCT05089734.

FIG 1.

Patient disposition: CONSORT diagram. ITT, intention-to-treat; SG, sacituzumab govitecan.

FIG 2.

OS. (A) OS in the intention-to-treat population (all randomly assigned patients). The HR and 95% CIs were calculated using the Cox proportional hazards model, adjusted for randomization stratification factors of histology and best response to last anti–PD-(L)1–containing regimen received. One-sided P value derived from the stratified log-rank test. (B) Subgroup analysis of OS. HR and 95% CIs for subgroup analysis are calculated using the unstratified Cox proportional hazards model without adjustment. Not otherwise specified histology is combined with nonsquamous. (C) OS in patients nonresponsive (SD/PD) to last anti–PD-(L)1–containing regimen. (D) OS in patients responsive (CR/PR) to last previous anti–PD-(L)1–containing regimen. The HRs and 95% CIs for the subgroup analyses were calculated using the unstratified Cox proportional hazards model without any adjustment. ^aRandomization stratification factors. CR, complete response; ECOG, Eastern Cooperative Oncology Group; EU, European Union; HR, hazard ratio; NR, not reached; OS, overall survival; PD, progressive disease; PR, partial response; SD, stable disease; SG, sacituzumab govitecan.

FIG 3.

PFS in the ITT population and OS in patients with SD/PD to last anti–PD-(L)1–containing regimen by histology. (A) PFS in the ITT population (all randomly assigned patients). The HR and 95% CIs for PFS were calculated using the Cox proportional hazards model, adjusted for randomization stratification factors of histology and best response to last anti–PD-(L)1–containing regimen received. (B) OS in patients with SD/PD to last anti–PD-(L)1–containing regimen and nonsquamous NSCLC. (C) OS in patients with SD/PD to last anti–PD-(L)1–containing regimen and squamous NSCLC. The HR and 95% CIs for subgroup analyses were calculated using the unstratified Cox proportional hazards model without any adjustment. Histology not otherwise specified is combined with nonsquamous. HR, hazard ratio; ITT, intention-to-treat; NSCLC, non–small cell lung cancer; OS, overall survival; PD, progressive disease; PFS, progression-free survival; SD, stable disease; SG, sacituzumab govitecan.