A study to evaluate the safety, tolerability, and efficacy of IBI939 in combination with sintilimab in patients with previously untreated locally advanced unresectable or metastatic PD-L1-selected non-small-cell lung cancer (NSCLC): Updated efficacy and safety results.

e14578 Background: According to studies in patients (pts) with solid tumors, T-cell immunoreceptor with Ig and ITIM domains (TIGIT) plays an important role in tumor immunosurveillance. The preliminary results showed that IBI939 plus sintilimab demonstrated improved PFS benefit and manageable safety profile in PD-L1 TPS ≥ 50% NSCLC pts with no prior systemic treatment (Ying Cheng et al. ESMO-IO, 2022). Here we report updated efficacy and safety data of this study. Methods: Eligible pts with systemic treatment-naïve, advanced or metastatic NSCLC, PD-L1 TPS ≥ 50%, and driver gene negative were enrolled and randomized 2:1 to IBI939 20 mg/kg plus sintilimab 200 mg IV Q3W (arm A) or sintilimab 200 mg monotherapy IV Q3W (arm B). The primary objective was to evaluate the ORR per RECIST v1.1. The secondary objectives include evaluation of PFS per RECIST v1.1, OS, and safety. Results: Of 42 pts enrolled, 28 pts (median age: 65; adenocarcinoma: n=19; brain metastasis: n=7) and 14 pts (median age: 58; adenocarcinoma: n=6; brain metastasis: n=1) were in arm A and arm B, respectively. As of Jan 1 st , 2023, with a median PFS follow-up of 12.2 months (95% CI, 11.1-13.9) in arm A and 11.3 months (95% CI, 10.8-13.6) in arm B. The median PFS per investigator was 13.2 months (95% CI, 6.7-16.5) in arm A vs 6.4 months (95% CI, 1.4-NA) in arm B (HR: 0.62; 95% CI, 0.26-1.43). All 42 pts were included for safety analysis. The overall safety profile was consistent with the latest previous report, with no new safety signals identified in each arm. The incidence of TRAEs was 96.4% vs 78.6% (5 pts in arm A and 6 pts in arm B experienced ≥ grade 3 events), respectively. Grade ≥ 3 immune-related AEs (determined by the investigator) were reported in 3 (10.7%) pts in arm A and 4 (28.6%) pts in arm B. All reported irAEs were manageable. One pt in each arm experienced TEAE leading to end of treatment. There was no TEAE leading to death happened in arm A. Two pts experienced grade 5 TEAE in arm B, which was unknown cause of death and respiratory failure. Conclusions: With longer follow-up time, IBI939 plus sintilimab demonstrated durable PFS benefit and manageable safety profile in PD-L1 TPS ≥ 50% NSCLC patients with no prior systemic treatment. Clinical trial information: NCT04672369 .