BeiGene Announces Late-Breaking Data at ESMO GI Showing Overall Survival Benefit for Tislelizumab Plus Chemotherapy in First-Line Advanced or Metastatic Esophageal Squamous Cell Carcinoma
June 30, 2022 at 04:00 AM EDT
BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, today announced new data from RATIONALE 306, a global Phase 3 trial evaluating tislelizumab plus chemotherapy in adult patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) without prior systemic treatment for advanced disease. Study results presented today as a late-breaking oral presentation at the 2022 European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer (Abstract #LBA-1) showed a statistically significant and clinically meaningful improvement in overall survival (OS) for patients receiving tislelizumab in combination with chemotherapy with a median OS of 17.2 months [95% CI: 15.8,20.1] versus 10.6 months [95% CI: 9.3,12.1] for those receiving chemotherapy plus placebo. The combination of tislelizumab with chemotherapy reduced the risk of death by 34% (HR=0.66 [95% CI: 0.54,0.80, p<0.0001]) compared to chemotherapy plus placebo.
“We are encouraged by the consistent, clinically meaningful benefit seen with tislelizumab and chemotherapy in key endpoints measuring efficacy and durability of response and across pre-specified subgroups in this 1L ESCC treatment setting,” said Mark Lanasa, M.D., Chief Medical Officer, Solid Tumors at BeiGene. “We sincerely appreciate the patients with ESCC from across the world who chose to participate in this study as we search for treatment options for this challenging condition.”
The OS benefit for tislelizumab plus chemotherapy was observed regardless of baseline PD-L1 expression. The median OS for patients with PD-L1 score ≥10% was 16.6 months [(95% CI: 15.3,24.4] in the tislelizumab plus chemotherapy group versus 10.0 months [95% CI: 8.6,13.0] for patients receiving chemotherapy plus placebo (HR=0.62; 95% CI, 0.44,0.86, p=0.0020). Analysis of patients with a PD-L1 score <10% showed a median OS of 16.7 months [95% CI: 13.0,20.1] for tislelizumab plus chemotherapy versus 10.4 months [95% CI: 9.1,13.0]; (HR=0.72 [95% CI: 0.55,0.94]) for chemotherapy plus placebo. This survival benefit was consistent across all other pre-specified subgroups, including race, region, and choice of chemotherapy.
“ESCC represents the majority of esophageal cancer worldwide, but unfortunately chemotherapy by itself provides a median survival in the range of only a year, so the survival benefit seen when tislelizumab was added to chemotherapy in our study is compelling” said Harry Yoon, MD, Associate Professor of Oncology and Chair of the Gastroesophageal Cancer Disease Group at Mayo Clinic in Rochester, Minnesota. “Additionally, it is encouraging to see a familiar safety and tolerability profile for the combination consistent with those established for chemotherapy in the community.”
Progression-free survival was significantly improved for the tislelizumab plus chemotherapy (7.3 months) group compared to chemotherapy alone (5.6 months) (HR=0.62 [95% CI: 0.52,0.75, p<0.0001]), Additional benefit in overall response (ORR) was seen with tislelizumab and chemotherapy compared to chemotherapy [ORR 63.5% vs 42.4%; p<0.0001) and the median duration of response was 7.1 months [95% CI: 6.1,8.1] for tislelizumab plus chemotherapy versus 5.7 months [95% CI: 4.4,7.1] chemotherapy alone.
The incidence of treatment-related adverse events (TRAEs) was similar in both arms; the most commonly reported TRAEs (≥ 20%) were anemia, decreased neutrophil count, decreased white blood cell count, decreased appetite, nausea and peripheral sensory neuropathy.
Tislelizumab is currently under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for advanced or metastatic ESCC 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. In January 2021, BeiGene announced a collaboration with Novartis to accelerate the clinical development and marketing of tislelizumab in North America, Europe, and Japan.
Tislelizumab is approved by the China National Medical Products Administration (NMPA) as a treatment for nine indications, including a recent approval for use in patients with locally advanced or metastatic ESCC who have disease progression or are intolerant to first-line standard chemotherapy. Tislelizumab is not approved for use outside of China.
About RATIONALE 306
The trial enrolled 649 patients at research centers across Asia-Pacific, Europe, and North America. Patients were randomized 1:1 to receive either tislelizumab plus chemotherapy or placebo plus chemotherapy.
About Esophageal Squamous Cell Carcinoma
Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.
BeiGene has initiated or completed more than 20 potentially registration-enabling clinical trials in 35 countries and regions, including 17 Phase 3 trials and four pivotal Phase 2 trials. More information on the clinical trial program for tislelizumab can be found at: https://www.beigene.com/en-us/science-and-product-portfolio/pipeline
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