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

Background

Prognosis of unresectable ESCC is poor, with median overall survival (OS) in 2^nd 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.

Methods

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).

Results

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: 1020MO

Efficacy

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

Conclusions

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.

Clinical trial identification

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Nate Connors, PhD CMPP, and Smitha Reddy, PhD, of Envision Pharma Group, and was funded by BeiGene.

Legal entity responsible for the study

BeiGene.

Funding

BeiGene.

Disclosure

D. Tougeron: Financial Interests, Personal, Advisory Board: AstraZeneca, Sanofi, AMGEN, MSD, Roche, Servier, Pierre Fabre, BMS, Bayer; Non-Financial Interests, Member of Board of Directors: Federation francophone de cancerologie digestive. S. Kim: Financial Interests, Personal, Advisory Board: Novartis, AstraZeneca, Lilly, DaeHwa Pharma, ISU Abx, Daiich-Sankyo, BeiGene, HLB Life Science, Samsung Bioepics, OBI pharma; Financial Interests, Personal, Invited Speaker: Legochem Bioscience; Financial Interests, Personal, Ownership Interest: Genopeaks, Neogene TC; Financial Interests, Institutional, Research Grant: Novartis, Sanofi-Genzyme, DongKook Pharm Co. E. Van Cutsem: Financial Interests, Personal, Advisory Board: AbbVie, ALX, Amgen, Array, Astellas, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi, GSK, Incyte, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Mirati, Novartis, Nordic, Pierre Fabre, Pfizer, Roche, Seattle Genetics, Servier, Takeda, Terumo, Taiho, Zymeworks; Financial Interests, Institutional, Research Grant: Amgen, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, Servier. R. Abdrashitov: Financial Interests, Other, Employment: BeiGene. R. Ge, J. Sun, J. Zhou: Financial Interests, Other, Employment: BeiGene. R. Xu: Financial Interests, Personal, Invited Speaker: BMS, MSD; Financial Interests, Personal, Advisory Board: Henrui, BeiGene, Astalas, Merck, Junshi. All other authors have declared no conflicts of interest.