Longer follow-up for survival and safety from the EVOKE-01 trial of sacituzumab govitecan (SG) vs docetaxel in patients (pts) with metastatic non-small cell lung cancer (mNSCLC).

Abstract

8599 Background: EVOKE-01 (NCT05089734) assessed the efficacy and safety of SG vs docetaxel in pts with mNSCLC that progressed after platinum-based chemotherapy and anti–PD-(L)1 (IO) treatment. The study did not meet statistical significance for overall survival (OS) at final analysis. Here, we report updated survival and safety outcomes after longer follow-up, providing insight into the tolerability of SG over a prolonged period of administration. Methods: Pts were randomized 1:1 to receive SG (n = 299; 10 mg/kg IV, days 1 and 8) or docetaxel (n = 304; 75 mg/m 2 IV, day 1) in 21-day cycles until progression or unacceptable toxicity. OS was the primary endpoint, while safety was a key secondary endpoint. Results: As of Oct 21, 2024, median follow-up was 23.5 months. Median exposure with SG vs docetaxel was 3.5 vs 2.3 months; 33.4% vs 17.7% of pts, respectively, were exposed to study drug for ≥6 months. The longer follow-up preserved the numerical improvement in OS favoring SG in the intent-to-treat population (HR 0.89, 95% CI: 0.74–1.07; P = .1028) and in subgroups of interest, including nonresponders to prior IO, and across squamous and nonsquamous histologies ( Table ). Most common any-grade treatment-emergent adverse events (TEAEs) with SG vs docetaxel were fatigue (57.8% vs 56.6%), diarrhea (52.7% vs 33.7%), and alopecia (43.6% vs 30.2%). In line with the primary analysis, 68.6% vs 76.0% of pts receiving SG vs docetaxel experienced grade ≥3 TEAEs, mainly neutropenia (25.3% vs 36.8%), fatigue (12.5% vs 9.7%), and diarrhea (10.5% vs 3.8%). Discontinuations due to TRAEs were seen in 7.4% vs 14.2% of pts receiving SG vs docetaxel. There were no additional AEs leading to death reported with longer follow-up (Table). Conclusions: Consistent with the final analysis, SG showed a numerical improvement in OS vs docetaxel. Long-term safety showed SG is well tolerated, consistent with minimal increase in AE rates since prior report and an improved safety profile over docetaxel, despite longer treatment exposure. Clinical trial information: NCT05089734 . Median OS, mo (95% CI) HR (95% CI) SG Doc Nonresponsive (SD/PD) to last IO n = 19211.8 (9.6–12.8)0.83 (0.66–1.04) n = 1918.3 (6.9–10.2) Responsive (CR/PR) to last IO n = 1069.7 (8.4–14.3)1.05 (0.78–1.43) n = 11310.8 (9.2–12.8) Squamous n = 8410.3 (8.1–13.2)0.89 (0.63–1.25) n = 809.2 (6.9–11.0) Nonsquamous n = 21511.6 (9.4–12.9)0.89 (0.72–1.11) n = 2249.9 (7.9–11.2) With prior therapy for AGA n = 1912.9 (7.2–23.9)0.63 (0.31–1.29) n = 257.0 (5.2–11.6) TEAE, % (safety population)Any gradeGrade ≥3Serious TEAEsLeading to dose reductionLeading to discontinuationTRAEs leading to discontinuationLeading to deathTRAEs leading to death n = 296 99.768.647.629.710.17.43.41.4 n = 288 98.376.044.439.216.714.24.21.0