CheckMate-9DW 4-year follow-up: Overall survival by depth of response and outcomes in long-term survivors.

Abstract

4104 Background: Nivolumab plus ipilimumab (NIVO + IPI) was globally approved as a first-line (1L) treatment for unresectable hepatocellular carcinoma (HCC) based on the phase 3 CheckMate 9DW trial (NCT04039607). We report 4-year follow-up results and overall survival (OS) by depth of response (DpR). Methods: Methods were reported previously (Yau T. Lancet 2025). Briefly, adults with previously untreated unresectable HCC were randomized 1:1 to receive NIVO + IPI (then NIVO for ≤ 2 years) or lenvatinib/sorafenib (LEN/SOR). OS analyses were done by best percentage change in tumor burden from baseline. We also present exploratory analyses on long-term survivors (survival ≥ 4 years after randomization). Results: A total of 668 patients (pts) were randomized to NIVO + IPI (n = 335) or LEN/SOR (n = 333); among 325 pts treated with LEN/SOR, 275 (85%) received LEN. At a median (range) follow-up of 52.5 (44.0–66.1) mo, NIVO + IPI continued to show OS benefit (95% CI) vs LEN/SOR (HR 0.78 [0.65–0.93]) with higher objective response rate (ORR; 95% CI) by blinded independent central review (BICR; 36% [31–42] vs 13% [10–17]) and more durable responses. Pts with deeper tumor reduction had numerically improved median OS on both NIVO + IPI and LEN/SOR; the trend was more pronounced with NIVO + IPI specifically in pts with tumor shrinkage ≥ 30% (Table). More pts treated with NIVO + IPI (n = 62) were long-term survivors vs pts treated with LEN/SOR (n = 33). In long-term survivors, ORR by BICR was higher with NIVO + IPI vs LEN/SOR (76% vs 24%), with higher rates of complete response (CR; 21% vs 6%; Table); median duration of response was not reached in either group. Among long-term survivors, median (range) treatment-free interval was 23.3 (0.1–56.6) mo with NIVO + IPI and 0.5 (0.1–54.0) mo with LEN/SOR; 26 of 62 (42%) and 2 of 33 (6%) patients, respectively, were off study treatment and remained free from subsequent treatment. Baseline characteristics and incidence of TRAEs in long-term survivors were consistent with all randomized pts. Conclusions: 1L NIVO + IPI continued to show sustained efficacy benefit vs LEN/SOR in unresectable HCC with no new safety concerns at the 4-year follow-up. These analyses suggest deeper responses with NIVO + IPI may be associated with improved survival outcomes. Long-term survivors treated with NIVO + IPI had higher ORR and CR rates vs LEN/SOR, and were more likely to remain free of subsequent treatment. These results reinforce NIVO + IPI as a 1L treatment for unresectable HCC. Clinical trial information: NCT04039607 . DpR, a % NIVO + IPI(n = 290) b LEN/SOR(n = 286) b Median OS (95% CI), mo Median OS (95% CI), mo −100 to ≤−60 NR (NE) NR (28.3–NE) −60 to ≤−30 31.1 (19.9–40.4) 20.9 (15.1–30.9) −30 to 20 17.0 (14.8–22.0) 20.5 (17.1–22.9) ≥20 14.3 (6.0–17.5) 7.8 (4.8–19.3) Best overall response in long-term survivors a NIVO + IPI (n = 62) LEN/SOR (n = 33) ORR (95% CI), % 76 (63–86) 24 (11–42) CR, % 21 6 a By BICR. b Response evaluable pts. NE, not estimable; NR, not reached.