1057P Long-term follow-up of a phase II study of tislelizumab (TIS) monotherapy in patients (pts) with previously treated, locally advanced, unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors

TIS is an anti-programmed cell death protein 1 monoclonal antibody engineered to minimize FcγR binding. Primary results from this single-arm, multicenter, open-label, phase 2 study (NCT03736889) evaluating TIS in pts with MSI-H/dMMR solid tumors showed a clinically meaningful objective response rate (ORR). Here, we report updated analysis with longer follow-up. Eligible adult participants had previously treated, locally advanced, unresectable/metastatic solid tumors with centrally confirmed MSI-H/dMMR, ≥1 measurable lesion (RECIST v1.1), and an ECOG performance status ≤1. Pts received TIS 200 mg intravenously once every 3 weeks until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was Independent Review Committee (IRC)-assessed ORR (RECIST v1.1). Secondary endpoints included overall survival (OS), IRC-assessed duration of response (DoR), progression-free survival (PFS), and disease control rate, and safety. Of 80 pts enrolled and treated in the study, 75 had measurable disease per IRC at baseline and were included in the efficacy-evaluable population. At data cutoff (Dec 5, 2022), median study follow-up was 28.9 months; minimum follow-up from last patient in to data cutoff was 28.1 months. Efficacy results are shown in the Table. ORR was 49.3%; median DoR, PFS, and OS were not reached. Treatment-emergent adverse events (TEAEs) ≥grade 3 occurred in 48 pts (60.0%); the most common was anemia, occurring in nine pts (11.3%). TEAEs leading to treatment discontinuation occurred in six pts (7.5%). With a minimum of 28.1 months’ follow-up, TIS-treated pts with previously treated MSI-H/dMMR solid tumors demonstrated a higher ORR compared with previous analysis, and durable improvements in DoR, PFS, and OS, with no new safety signals.Table: 1057PTumor Response in the Efficacy-evaluable PopulationAll tumor types (N=75)ORR, n (%)37 (49.3)95% CI37.6, 61.1Best overall response, n (%)Complete response10 (13.3)Partial response27 (36.0)mDoR,a mo (95% CI)NR (NE, NE)24-month DoR rate, % (95% CI)97.0 (80.4, 99.6)mPFS,a mo (95% CI)NR (7.5, NE)24-month PFS rate, % (95% CI)56.7 (44.1, 67.4)mOS, mo (95% CI)NR (33.3, NE)24-month OS rate, % (95% CI)68.6 (56.6, 77.9)aIRC-assessed per RECIST v1.1 OS analysis is based on safety analysis population (N=80). CI, confidence interval; m, median; mo, months; NE, not estimable; NR, not reached. Open table in a new tab