On April 20, 2023 BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported that the global RATIONALE 305 trial met its primary endpoint of overall survival, with tislelizumab in combination with chemotherapy demonstrating superior overall survival (OS) compared with chemotherapy in patients with advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, regardless of PD-L1 status (Press release, BeiGene, APR 20, 2023, View Source [SID1234630342]). No new safety signals were identified for tislelizumab.
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BeiGene previously announced superior OS for the combination compared with chemotherapy in the PD-L1 high group at a planned interim analysis1 and the trial continued according to pre-specified statistical hierarchy testing. At the final analysis, tislelizumab, in combination with chemotherapy, demonstrated superior OS compared with chemotherapy in the intent-to-treat (ITT) population. Results will be submitted for presentation at an upcoming medical conference.
"At the recent ASCO (Free ASCO Whitepaper) GI meeting, we presented results from an interim analysis demonstrating a statistically significant and clinically meaningful improvement in overall survival in the high PD-L1 expression group in RATIONALE 305 and we are pleased that the final analysis demonstrated a significant survival benefit and consistent safety profile in the entire study population," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "Gastric cancer is the fifth most common cancer globally, and the prognosis for patients with advanced or metastatic conditions remains inadequate; these data support tislelizumab combined with chemotherapy as a potential first-line treatment option for patients with locally advanced, unresectable or metastatic gastric or gastroesophageal junction cancer."
Tislelizumab is currently under review by the U.S. Food and Drug Administration and the European Medicines Agency (EMA) for advanced or metastatic esophageal squamous cell carcinoma after prior chemotherapy. The EMA is also reviewing tislelizumab for advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated advanced or metastatic NSCLC.
Tislelizumab is approved in 10 indications in China, including a recent approval for use in combination with fluoropyrimidine and platinum chemotherapy for the first-line treatment of patients with locally advanced unresectable or metastatic G/GEJ adenocarcinoma with high PD-L1 expression. The 2023 update to the National Reimbursement Drug List issued by China’s National Healthcare Security Administration includes nine reimbursed indications for tislelizumab. Tislelizumab is not currently approved for use outside of China.
About RATIONALE 305 (NCT03777657)
RATIONALE 305 is a randomized, double-blind, placebo-controlled, global Phase 3 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 G/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 ≥ 5% by VENTANA SP263 assay, assessed by blinded independent central laboratory. OS analysis in ITT population would be performed only after the OS analysis in the PD-L1 high population is 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 (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium. In patients with G/GEJ adenocarcinoma 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 identified1.
About Tislelizumab
Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.
An expansive global clinical trial program supports tislelizumab development, with 21 registration-enabling clinical trials and more than 11,800 subjects enrolled across the world. More information on the clinical trial program for tislelizumab can be found at:View Source