Iparomlimab (QL1604) in patients (pts) with unresectable/metastatic deficient mismatch repair (dMMR)/microsatellite instability high (MSI-H) solid tumors: A single-arm, multicenter, pivotal, phase II study.

3578 Background: Iparomlimab, a novel anti-PD-1 antibody, demonstrated robust anti-tumor activity and well tolerated safety in pts with unresectable/metastatic dMMR/MSI-H solid tumors. At median follow-up of 17 mo, iparomlimab treatment demonstrated durable clinical benefit. Methods: This phase II study (NCT04326829) enrolled pts pathologically diagnosed as dMMR/MSI-H unresectable/metastatic solid tumors. Pts received iparomlimab (200 mg, iv, Q3W; 3 mg/kg for pts with body weight <40 kg). The primary endpoint was confirmed objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST 1.1. Eligible pts, who were enrolled and received at least 1 cycle of treatment, were included in the intention to treat (ITT) set. Among them, relapsed/refractory pts were included in the full analysis set (FAS) as primary efficacy analysis population. The FAS included pts with advanced colorectal cancer (CRC) failed from fluoropyrimidine, oxaliplatin, and irinotecan, pts with gastric cancer failed from at least two lines of standard of care, and other solid tumors failed from at least one prior treatment. Results: From Jun 19, 2020 to Jan 12, 2023, 120 pts were enrolled in ITT, with 60 pts in FAS. 117 (97.5%) pts were featured with stage IV disease. The median prior therapy lines were 2.0 in both ITT and FAS, respectively. CRC was diagnosed in 80 (66.7%) pts in ITT and 38 (63.3%) pts in FAS. As of Jan 20, 2024, the ORR were 58/120 (48.3%; 95% CI: 39.1%–57.6%) with 12 (10.0%) complete response (CR) and 46 (38.3%) partial response (PR) in ITT, and 30/60 (50.0%, 36.8%–63.2%) with 3 (5.0%) CR and 27 (45.0%) PR in FAS. In CRC pts, the ORR per IRRC were 37/80 (46.3%) and 22/38 (57.9%) in ITT and FAS, respectively. (Efficacy shown in Table) TRAEs of any grade occurred in 95 (79.2%) pts. The most frequent TRAE of any grade and grade ≥3 TRAE were both anemia, with incidence of 26.7% and 5.0%, respectively. irAEs of any grade were reported in 39/120 (32.5%) pts, with the most common occurring irAEs of hpothyroidism (12/120, 10.0%). TRSAEs occurred in 13/120 (10.8%) patients. No iparomlimab-related death occurred. Conclusions: At 17-mo follow-up, iparomlimab showed encouraging efficacy with durable response and tolerable safety in patients with unresectable/metastatic dMMR/MSI-H solid tumors in ITT and FAS. Clinical trial information: NCT04326829 . [Table: see text]