Ociperlimab and tislelizumab in advanced esophageal squamous cell carcinoma (AdvanTIG-203): a phase II study.

Patients with esophageal squamous cell carcinoma (ESCC) have an unmet need for new therapies that improve survival. In this phase II trial, patients received ociperlimab and tislelizumab (A) or placebo and tislelizumab (B) (NCT04732494). The primary endpoint was objective response rate (ORR) assessed by the investigator per RECIST v1.1. A total of 125 patients were randomized to A (N = 62) and B (N = 63). The primary endpoint was not met, with an ORR (95% confidence interval [CI]) assessed by the investigator of 30.6% (19.6-43.7) for A and 20.6% (11.5-32.7) for B (stratified risk difference: 9.9% [95% CI - 5.4 to 25.3]; stratified 2-sided p = 0.2114). At the final analysis, median OS (95% CI) was 10.2 (7.9-19.5) months for A and 9.3 (6.4-14.8) months for B (stratified HR [95% CI]: 0.92 [0.58-1.45]). A total of 25.8% (16/62) and 20.6% (13/63) of patients in A and B, respectively, experienced grade ≥3 treatment-related treatment-emergent adverse events. Exploratory biomarker analyses showed that patients with an inflamed tumor microenvironment, shown by the enriched expression of natural killer (NK) cells, T cells, macrophages, dendritic cells, and B-cell signatures, and NK cell signature enrichment, may benefit from ociperlimab plus tislelizumab. Adding ociperlimab to tislelizumab did not provide significant efficacy improvement in recurrent/metastatic second-line ESCC; the addition of ociperlimab to tislelizumab was generally well-tolerated. Trial registration: Clinicaltrials.gov: NCT04732494.