CStone Pharmaceuticals announced that the data from a Phase 3 clinical trial (GEMSTONE-304), evaluating sugemalimab in combination with chemotherapy as the first-line treatment for unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC), has been presented in an oral session at the ESMO World Congress on Gastrointestinal Cancer 2023 (ESMO GI 2023). Key Highlights: The GEMSTONE-304 study has met its pre-specified dual primary endpoints. Sugemalimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) assessed by Blinded Independent Central Review (BICR) and overall survival (OS); Sugemalimab would be the first anti-PD-L1 monoclonal antibody worldwide as the first-line treatment for unresectable locally advanced, recurrent, or metastatic esophageal squamous cell carcinoma (ESCC), if approved.

The GEMSTONE-304 study is a randomized, double-blind, multi-center, placebo-controlled Phase 3 registrational clinical trial, designed to evaluate the efficacy and safety of sugemalimab in combination with 5-fluorouracil plus cisplatin as the first-line treatment in patients with unresectable locally advanced, recurrent, or metastatic ESCC. The dual primary endpoints are PFS assessed by BICR and OS. Secondary endpoints include investigator-assessed PFS, BICR- and investigator-assessed objective response rate (ORR) and duration of response (DoR), etc.

The data presented at ESMO GI 2023 is based on the final analysis of PFS and the interim analysis of OS with a cutoff date of October 7, 2022. The results demonstrate that the GEMSTONE-304 study has met its predefined dual endpoints. Sugemalimab in combination with chemotherapy demonstrated a statistically significant and clinically meaningful improvement in the BICR-assessed PFS and OS.

Key findings include: The BICR-assessed median PFS in the sugemalimab treatment group is 6.2 months compared with 5.4 months in the placebo group, with a hazard ratio (HR) of 0.67 (95% CI, 0.54-0.82), and a p-value of 0.0002; The median OS in the sugemalimab treatment group is 15.3 months compared with 11.5 months in the placebo group, with an HR of 0.70 (95% CI, 0.55-0.90), and a p-value of 0.0076; Subgroup analysis demonstrates consistent clinical benefits were observed across almost all predefined subgroups, including PD-L1 expression status; The BICR- assessed ORR is 60.1% vs 45.2%, with a difference of 14.9% (95% CI, 5.9%-23.8%), and a p-value of 0.0011. The DoR is 6.0 months vs 4.5 months; Sugemalimab in combination with chemotherapy shows good tolerability and safety, with no new safety signal observed.