Late-breaking data at ESMO showing tislelizumab plus chemotherapy significantly improved overall survival at final analysis in first-line advanced gastric or gastroesophageal junction adenocarcinoma.- BeiGene

No new safety signals were identified. Study results will be featured as a late-breaking oral presentation on October 21 at 5:25 p.m. CEST at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract #LBA80).

“Gastric cancer is a devastating disease that affects millions of people worldwide. Unfortunately, patients with advanced or metastatic conditions have a poor prognosis and urgently need more treatment options in the first-line setting,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “These data show that tislelizumab plus chemotherapy resulted in significant overall survival improvement compared with chemotherapy alone in the intent-to-treat patient group. These results and positive findings build upon the data presented earlier this year in the high PD-L1 expression group and add to the growing body of evidence demonstrating the potential for tislelizumab to help patients with advanced gastric cancer or gastroesophageal junction cancer.”

In the final analysis of 997 intent-to-treat patients from the Phase III RATIONALE 305 trial, tislelizumab plus chemotherapy (oxaliplatin 130 mg/m2 IV Q3W (day 1) and oral capecitabine 1000 mg/m2 twice daily (days 1-14) Q3W (XELOX), or cisplatin 80 mg/m2 IV Q3W (day 1) and 5-fluorouracil 800 mg/m2/day IV (days 1-5) Q3W (FP)) showed a median OS of 15.0 months compared with an OS of 12.9 months for chemotherapy alone (HR: 0.80 [95% CI: 0.70, 0.92]; P = 0.0011) in first line advanced GC/GEJC.

“The data from the RATIONALE 305 study suggest that tislelizumab plus chemotherapy represents a potential new first-line treatment option for patients with advanced GC/GEJC regardless of PD-L1 expression status,” said Rui-Hua Xu, M.D., Ph.D., Director of the Cancer Control Center of Sun Yat-sen University and principal investigator for the RATIONALE 305 trial. “Tislelizumab plus chemotherapy provided significant and clinically meaningful overall survival benefit versus chemotherapy in all randomized patients with previously untreated, HER2-negative advanced GC/GEJC.”

In the trial, tislelizumab plus chemotherapy was associated with a higher objective response rate (ORR) (47.3% vs. 40.5%) and median duration of response (mDoR) (8.6 months vs. 7.2 months) compared to placebo plus chemotherapy alone. Median progression-free survival (PFS) for tislelizumab plus chemotherapy was 6.9 months vs. 6.2 months respectively; (HR: 0.78 [95% CI: 0.67, 0.90]).

About RATIONALE 305 (NCT03777657): RATIONALE 305 is a randomized, double-blind, placebo-controlled, global Phase III trial comparing the efficacy and safety of tislelizumab combined with platinum and fluoropyrimidine chemotherapy and placebo combined with platinum and fluoropyrimidine chemotherapy as a first-line treatment for patients with advanced unresectable or metastatic GC/GEJ adenocarcinoma. A total of 997 patients from 13 countries and regions across the world were enrolled and randomized 1:1 to receive either tislelizumab or placebo in combination with chemotherapy. The primary endpoint for the trial is OS, with prespecified hierarchy testing for the PD-L1 high population followed by the ITT population. High PD-L1 expression is defined as PD-L1 score greater than 5% by VENTANA SP263 assay, assessed by blinded independent central laboratory. OS analysis in the ITT population would be performed only after the OS analysis in the PD-L1 high population was demonstrated to be statistically significant, favoring the tislelizumab and chemotherapy arm. Secondary endpoints include progression-free survival, overall response rate, duration of response, and safety.

Interim results were shared in an oral presentation at the 2023 ASCO Gastrointestinal Cancers Symposium. In patients with GC/GEJC with high PD-L1 expression, tislelizumab plus chemotherapy demonstrated statistically significant and clinically meaningful improvement in OS versus placebo plus chemotherapy [median OS: 17.2 vs 12.6 months; HR 0.74 (95% CI 0.59, 0.94); P=0.0056] with a manageable safety profile, and no new safety signals were identified.