Claudin18.2-specific CAR T cells (Satri-cel) versus treatment of physician's choice (TPC) for previously treated advanced gastric or gastroesophageal junction cancer (G/GEJC): Primary results from a randomized, open-label, phase II trial (CT041-ST-01

4003 Background: Claudin18.2 (CLDN18.2) has emerged as a promising therapeutic target in G/GEJC. Recently reported results showed CT041/satricabtagene autoleucel (satri-cel), an autologous CLDN18.2-specific CAR T-therapy, had encouraging efficacy in previously treated patients (pts) with advanced G/GEJC. Now we report the primary results from the phase II pivotal trial (CT041-ST-01, NCT04581473). Methods: In this open-label, multicenter, randomized controlled trial (RCT) conducted in China, CLDN18.2 positive, advanced G/GEJC pts with failure to at least 2 prior lines of treatment, were randomized (2:1) to satri-cel arm or TPC arm. For satri-cel arm, satri-cel dose of 250 ×10 6 cells were infused up to 3 times. For TPC arm, one of the standard of care (SOC) drugs (apatinib, paclitaxel, docetaxel, irinotecan or nivolumab) was given per physician's decision. Those who experienced disease progression or drug intolerance in TPC arm could receive subsequent satri-cel, if eligible. The primary endpoint was PFS assessed by the Independent Review Committee (IRC). Key secondary endpoint was OS. Data cutoff date was Oct 18, 2024. Results: From Mar 29, 2022 to Aug 16, 2024, a total of 156 pts were randomized to satri-cel arm (n = 104) or TPC arm (n = 52). Twenty pts in TPC arm received subsequent satri-cel. Median number of prior systemic therapies was 2 in both arms, and 26.9% vs 19.2% had received ≥3 lines; 69.2% vs 59.6% had peritoneal metastasis; 71.2% vs 65.4% were Lauren diffuse/mixed type. The median follow-up time of PFS and OS was 8.90 and 12.29 months (m). In ITT population, satri-cel arm showed significant improvement in mPFS by IRC (3.25m vs 1.77m; HR 0.366, 95% CI: 0.241, 0.557; p < 0.0001) and an obvious trend for longer mOS (7.92m vs 5.49m; HR 0.693, 95% CI: 0.457, 1.051; one-sided p = 0.0416) than TPC arm. Moreover, in 136 pts receiving study drug (mITT, satri-cel 88 pts vs TPC 48 pts), mPFS by IRC was 4.37m vs 1.84m, HR 0.304 (95% CI: 0.195, 0.474) and mOS was 8.61m vs 5.49m, HR 0.601 (95% CI: 0.385, 0.939). Notably, mOS of TPC pts with satri-cel was 9.20m. Among all pts receiving satri-cel (n = 108) vs TPC pts without satri-cel (n = 28), mOS was 9.17m vs 3.98m, HR 0.288 (95% CI: 0.169, 0.492). A summary of study drug-related adverse events (TRAEs) is shown in the Table. Conclusions: This is the first confirmatory RCT of CAR T-therapy in solid tumors. Satri-cel demonstrated significant PFS improvement and an obvious OS benefit with a manageable safety profile. These results support satri-cel as a potential new SOC for advanced G/GEJC. Clinical trial information: NCT04581473 . Safety, n (%) Satri-cel(n=88) TPC(n=48) TRAEs 88 (100) 44 (91.7) Serious TRAEs 31 (35.2) 12 (25.0) TRAE leading to death 1 (1.1) a 1 (2.1) b CRS 84 (95.5) 0 Grade 1-2 80 (90.9) 0 Grade 3 4 (4.5) 0 ICANS 0 0 a disseminated intravascular coagulation; b coagulopathy.