1020MO AdvanTIG-203: Phase II Randomized, Multicenter Study of Ociperlimab (OCI) + Tislelizumab (TIS) in Patients (pts) with Unresectable, Locally Advanced, Recurrent/metastatic Esophageal Squamous Cell Carcinoma (ESCC) and Programmed Cell Death-Ligand 1 (PD-L1) Positivity

Prognosis of unresectable ESCC is poor, with median overall survival (OS) in 2nd line (2L) of ∼10 months. Anti-PD-1 agents, including TIS, have demonstrated an OS increase, albeit still unsatisfactory, in unresectable ESCC pts. In preclinical studies and clinical studies of other tumors, coinhibition of T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) and PD-1 enhances antitumor activity of anti-PD-1. AdvanTIG-203 (NCT04732494) is investigating efficacy/safety of TIS +/- OCI (anti-TIGIT) in advanced ESCC pts, progressing on/after 1st line (1L) systemic therapy. Adult ESCC pts with PD-L1 tumor area positivity (TAP) ≥10% and progression on/after 1L systemic therapy were randomized (1:1) to OCI 900 mg + TIS 200 mg (O+T) or placebo + TIS (P+T) every 3 weeks until progression, unacceptable toxicity, or withdrawal. Primary endpoint was investigator (INV)-assessed objective response rate (ORR). Secondary endpoints included progression free survival (PFS). As of 1 Feb 2023, 125 pts (median age 64 years; 88.8% male) were randomized to O+T (n=62) or P+T (n=63). INV-assessed ORR was 30.6% with O+T vs. 20.6% with P+T; hazard ratio (HR) of INV-assessed PFS was 0.93 (95% CI: 0.61, 1.43) (Table). Incidence of pts with ≥1 any adverse event (AE) was comparable between O+T (93.5%) and P+T (95.2%); most common AE was anemia (O+T: 25.8%; P+T: 28.6%). Respective AE rates for O+T and P+T were 41.9% and 41.3% grade ≥3 AEs, 41.9% and 39.7% serious AEs, 9.7% and 15.9% AEs that led to treatment discontinuation, 45.2% and 30.2% immune-related AEs, and 0% and 3.2% treatment-related fatal AEs.Table: 1020MOEfficacyO+T (n=62)P+T (n=63)ORRa, % (95% CI)INVb30.6 (19.6, 43.7)20.6 (11.5, 32.7)Pc,d=0.2114IRCe32.3 (20.9, 45.3)25.4 (15.3, 37.9)Pc,d=0.4209OSe,f (months), median (95% CI)10.1 (7.1, NE)9.3 (6.0, NE)HRc (95% CI): 0.93 (0.55, 1.58) Pc,g=0.3977PFSe (months), median (95% CI)INV3.4 (1.8, 5.1)3.5 (1.9, 4.1)HRc (95% CI): 0.93 (0.61, 1.43)IRC3.6 (2.7, 5.1)2.8 (1.9, 6.9)HRc (95% CI): 1.01 (0.64, 1.59)Median follow-up was 7 months. IRC, independent review committee; NE, not estimable aConfirmed per RECIST v1.1bPrimary endpoint cStratified d2-sided; by Cochran-Mantel-Haenszel method eSecondary endpoint fStill immature (event rate 45.6%) g1-sided; by log-rank test Open table in a new tab Median follow-up was 7 months. IRC, independent review committee; NE, not estimable aConfirmed per RECIST v1.1 bPrimary endpoint cStratified d2-sided; by Cochran-Mantel-Haenszel method eSecondary endpoint fStill immature (event rate 45.6%) g1-sided; by log-rank test In 2L therapy of advanced ESCC pts with PD-L1 TAP ≥10%, O+T showed tolerable safety profile and trend toward better ORR, but similar PFS vs. P+T.