New data from the phase 3 RATIONALE 305 trial of tislelizumab with chemotherapy show potential of the combination for patients with advanced gastric cancer or gastroesophageal junction adenocarcinoma.
Tislelizumab (BGB-A317) with chemotherapy led to significant improvements in overall survival (OS) in the intent-to-treat (ITT) population as a first-line treatment for patients with advanced gastric cancer or gastroesophageal junction (GEJ) adenocarcinoma (GEJ), according to the final analysis of the phase 3 RATIONALE 305 trial (NCT03777657).1
Findings showed that tislelizumab with chemotherapy demonstrated a median OS of 15.0 months compared with an OS of 12.9 months for chemotherapy alone (hazard ratio [HR], 0.80; 95% CI, 0.70-0.92; P =.0011) when given in the first-line for patients with advanced gastric and GEJ adenocarcinoma. The combination of tislelizumab plus chemotherapy showed a median progression-free survival (PFS) rate of 6.9 months vs 6.2 months among patients treated with placebo plus chemotherapy (HR, 0.78; 95% CI, 0.67-0.90).
Additionally, patients treated with the combination had a higher objective response rate (ORR) at 47.3% compared with those given placebo and chemotherapy at 40.5%, and the median duration of response (mDOR) was 8.6 months with tislelizumab and chemotherapy vs 7.2 months for placebo plus chemotherapy alone. For safety, no new safety signals were identified.
“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,” said Mark Lanasa, MD, PhD, chief medical officer, Solid Tumors at BeiGene, in a press release.1
The randomized, double-blind, placebo-controlled, global, phase 3 RATIONALE 305 trial is evaluating the efficacy and safety of tislelizumab in combination with platinum and fluoropyrimidine chemotherapy compared with placebo combined with platinum and fluoropyrimidine chemotherapy as a first-line treatment for patients with advanced unresectable or metastatic gastric and GEJ adenocarcinoma.2
Patients were enrolled from 13 countries and regions across the globe and randomized in a 1:1 fashion to receive either tislelizumab or placebo in combination with chemotherapy. A total of 997 ITT patients were enrolled and included in the final analysis of the study.1,2
Once enrolled, patients were given tislelizumab with chemotherapy, consisting of oxaliplatin 130 mg/m2 via intravenous (IV) infusion every 3 weeks (Q3W) given on day 1 with oral capecitabine 1000 mg/m2 twice daily on days 1-14 Q3W, or cisplatin 80 mg/m² IV Q3W on day 1 with 5-fluorouracil 800 mg/m2/day IV on days 1-5 Q3W.
The primary end point being evaluated in the trial is OS, with prespecified hierarchy testing for the PD-L1 high population followed by the ITT population, and secondary end points consist of PFS, ORR, DOR, and safety.
Previously, at the 2023 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, interim results from the trial were presented and showed that patients with gastric and GEJ adenocarcinoma with high PD-L1 expression had improvements in OS when treated with tislelizumab plus chemotherapy vs placebo and chemotherapy.3 The combination with tislelizumab showed a significant and clinically meaningful improvement in OS at 17.2 months vs 12.6 months with placebo and chemotherapy (HR, 0.74; 95% CI, 0.59-0.94; P =.0056)].
Further, the combination with tislelizumab exhibited a manageable safety profile, and no new safety signals were identified.1
Additional results from the study will be featured as a late-breaking oral presentation at the European Society for Medical Oncology Congress 2023.
“The data from the RATIONALE 305 study suggest that tislelizumab plus chemotherapy represents a potential new first-line treatment option for patients with advanced [gastric]/GEJ [adenocarcinoma] regardless of PD-L1 expression status,” said Rui-Hua Xu, MD, PhD, director of the cancer control center of Sun Yat-sen University and principal investigator for the RATIONALE 305 trial, in a press release.1 “Tislelizumab plus chemotherapy provided significant and clinically meaningful overall survival benefit versus chemotherapy in all randomized patients with previously untreated, HER2-negative advanced [gastric]/GEJ [adenocarcinoma].”