T-cell immunoreceptor with Ig and ITIM domains (TIGIT) plays an important role in tumor immunosurveillance in addition to well-established immunosuppressive checkpoint receptors such as PD-1 and CTLA-4. We report the preliminary safety and anti-tumor activity of IBI939 (anti-TIGIT mAb) in combination with sintilimab (anti-PD-1 mAb) in patients (pts) with previously untreated locally advanced unresectable or metastatic PD-L1-selected NSCLC.
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.
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 June 30th, 2022, among 40 response-evaluable NSCLC pts (27 in arm A vs 13 in arm B), the confirmed ORR was 66.7% (95% CI, 46.0-83.5) vs 61.5% (95% CI, 31.6-86.1)(arm A vs B). Nine pts with the event (progressive disease or death) had occurred in both arms. The median PFS was not reached (95% CI, 6.8-NA) in arm A vs 6.0 months (95% CI, 1.4-NA) in arm B (HR: 0.43; 95% CI, 0.17-1.10). The incidence of TRAEs was 85.7% vs 71.4% (2 and 5 pts experienced ≥ grade 3 events in each arm), respectively. The most common TRAEs were hypothyroidism (35.7%), aspartate aminotransferase increased (21.4%), blood urea increased (17.9%), hyperthyroidism (17.9%) in arm A. Immune-related AEs (determined by the investigator) were reported in 64.3% of pts in arm A and 50.0% of pts in arm B.
IBI939 plus sintilimab demonstrated improved PFS benefit and manageable safety profile in PD-L1 TPS ≥ 50% NSCLC patients with no prior systemic treatment.
NCT04672369.
Innovent Biologics, Inc., Suzhou, Jiangsu, China.
Innovent Biologics, Inc., Suzhou, Jiangsu, China.
Y. Chen, G. Han, J. Ye: Financial Interests, Personal, Sponsor/Funding, Employment: Innovent Biologics, Inc. All other authors have declared no conflicts of interest.