Pucotenlimab in high microsatellite instability/mismatch repair–defificient (MSI-H/ dMMR) solid tumors: Results update from a multicenter, phase II, open-label study.

Abstract

e14589 Background: Pucotenlimab, an anti-PD-1 antibody, demonstrated robust antitumor activity in patients (pts) with MSI-H/dMMR, based on findings from the phase II study 1 . Here, we present the long-term survival results and updated safety profile. Methods: Eligible pts were aged ≥18 years with histologically/cytologically confirmed advanced MSI-H/dMMR solid tumors, who had failed at least 1 line of standard systemic therapy. MSI-H/ dMMR status was assessed in a central lab. Pts received pucotenlimab 200 mg Q3W until disease progression, unacceptable toxicity, or patient withdrawal. The primary endpoint was the Independent Review Committee (IRC) evaluated ORR per RECIST1.1, the secondary endpoints included DoR, PFS, OS, and safety. The tumor response data was collected until 36 months for each subject. Results: 100 pts were enrolled from Oct 2018 to Dec 2020, the most common cancer types were colorectal cancer (CRC, N=71GC, N=10; EC, N=7; Other, N=12). By the cut-off date (Sep 19, 2024), median follow-up period was 43.8m (range: 0.3, 61.7). The updated ORR by IRC was 50.0% (95%CI: 39.8, 60.2, CR=12%). The mPFS was 33.8m (95%CI: 7.1, NR), while the 36-m rates were 49.7% (95%CI: 39.2, 59.3). The mDoR was not reached, 36-m DoR rate was 81.1% (95%CI: 66.7, 89.7). The mOS was 55.9 m (95%CI: 55.9, NR), with the 60-m OS rate 46.3% (95%CI: 19.1, 69.9). Pts in the CRC cohort had optimizing clinical benefits, with an ORR by IRC of 57.7% (95%CI: 46.8, 70.7), a 36-m PFS rate of 52.5% (95%CI: 39.9, 63.7), and a longer mOS was 55.9 m (95%CI: 55.9, NR). The 60-m OS rate was 44.3% (95%CI: 10.7, 74.3). The common treatment-related adverse events (TRAEs) of any grade included AST increased (28.0%), ALT increased (26.0%), and anemia (24.0%). TRAEs ≥ Grade 3 were reported in 24 pts (24.0%). No new safety signals were identified in this analysis, and patients had good tolerance to long-term treatment. Conclusions: Pucotenlimab as ≥2L therapy for advanced MSI-H/dMMR solid tumors demonstrates durable OS and PFS benefit. The updated, long-term follow-up data confirmed durable clinical benefit of pucotenlimab in this patient population, especially for CRC pts. References:1. Zhang B, et al. Cell Rep Med. 2023;4(12):101301. Clinical trial information: NCT03704246 .