• First-line tislelizumab plus chemotherapy demonstrated a median overall survival of 15.0 months versus 12.9 months for placebo plus chemotherapy in the intent-to-treat group of the Phase 3 RATIONALE 305 trial
• The safety profile for tislelizumab in combination with chemotherapy was manageable and in line with the known safety profile of anti-PD-1 antibodies

BASEL, Switzerland & BEIJING & CAMBRIDGE, Mass. / Oct 17, 2023 / Business Wire / BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, today announced results from the final analysis of the Phase 3 RATIONALE 305 trial showing tislelizumab plus chemotherapy significantly improved overall survival (OS) in the intent-to-treat (ITT) population as a first-line treatment for patients with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC). 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 3 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 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 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 ≥ 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 identifiedⁱ.

About Tislelizumab

Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody, with high affinity and binding specificity against PD-1, specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. 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.^ii,iii,iv,v

The tislelizumab development program encompasses 21 registration-enabling clinical trials in more than 30 countries and regions. To date, BeiGene has announced positive readouts from 10 Phase 3 pivotal studies across multiple tumor types and disease settings, such as NSCLC, small cell lung cancer, gastric cancer, ESCC, hepatocellular cancer, and nasopharyngeal cancer. More information on the clinical trial program for tislelizumab can be found at: https://www.beigene.com/en-us/science-and-product-portfolio/pipeline.

Tislelizumab is currently under review by the U.S. Food and Drug Administration (FDA) and received approval by the European Commission for advanced or metastatic ESCC after prior chemotherapy. Additionally, the FDA recently accepted for review a Biologics License Application for tislelizumab as a first-line treatment for patients with unresectable, recurrent, locally advanced, or metastatic ESCC. The European Medicines Agency (EMA) is reviewing a marketing authorization application for tislelizumab as a treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated locally advanced or metastatic NSCLC.

Regulatory submissions for tislelizumab are also under review by authorities in Australia, Brazil, China, Korea, Israel, New Zealand, Singapore, Switzerland, and the U.K. Tislelizumab is approved for 11 indications in China and is the leading PD-1 inhibitor in the country.

About BeiGene

BeiGene is a global biotechnology company that is discovering and developing innovative oncology treatments that are more affordable and accessible to cancer patients worldwide. With a broad portfolio, we are expediting development of our diverse pipeline of novel therapeutics through our internal capabilities and collaborations. We are committed to radically improving access to medicines for far more patients who need them. Our growing global team of more than 10,000 colleagues spans five continents, with administrative offices in Basel, Beijing, and Cambridge, U.S. To learn more about BeiGene, please visit www.beigene.com and follow us on LinkedIn and X (formerly known as Twitter).

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the potential for tislelizumab to help patients with advanced gastric cancer or gastroesophageal junction cancer; the future development, regulatory filing, approval and commercialization of tislelizumab; and BeiGene’s plans, commitments, aspirations, and goals under the heading “About BeiGene.” Actual results may differ materially from those indicated in the forward-looking statements as a result of various important factors, including BeiGene's ability to demonstrate the efficacy and safety of its drug candidates; the clinical results for its drug candidates, which may not support further development or marketing approval; actions of regulatory agencies, which may affect the initiation, timing, and progress of clinical trials and marketing approval; BeiGene's ability to achieve commercial success for its marketed medicines and drug candidates, if approved; BeiGene's ability to obtain and maintain protection of intellectual property for its medicines and technology; BeiGene's reliance on third parties to conduct drug development, manufacturing, commercialization, and other services; BeiGene’s limited experience in obtaining regulatory approvals and commercializing pharmaceutical products and its ability to obtain additional funding for operations and to complete the development of its drug candidates and achieve and maintain profitability; and those risks more fully discussed in the section entitled “Risk Factors” in BeiGene’s most recent quarterly report on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in BeiGene's subsequent filings with the U.S. Securities and Exchange Commission. All information in this press release is as of the date of this press release, and BeiGene undertakes no duty to update such information unless required by law.

ⁱ Moehler, Markus H., et al. "Rationale 305: Phase 3 study of tislelizumab plus chemotherapy vs placebo plus chemotherapy as first-line treatment (1L) of advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJC)." Journal of Clinical Oncology 41, no. 4_suppl (February 01, 2023) 286-286 DOI: 10.1200/JCO.2023.41.4_suppl.286
ⁱⁱ Desai J et al. Abstract Book of the 42 ESMO Congress (ESMO 2017). Annals of Oncology 2017. Volume 28, supplement 5; v122–v141.
ⁱⁱⁱ Zhang T et al. “The binding of an anti-PD-1 antibody to Fcγ has a profound impact on its biological functions.” Cancer Immunology, Immunotherapy. Volume 67, issue 7 (July 2018) 1079–1090
^iv Arlauckas SP et al. “In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy.” Science Translation Medicine; 2017 May 10;9(389):eaal3604. DOI: 10.1126/scitranslmed.aal3604
^v Dahan R et al. “FcyRs Modulate the Anti-tumor Activity of Antibodies Targeting the PD-1/PD-L1 Axis.” Cancer Cell. Volume 28, issue 3 (September 2015); 285–295. DOI:10.1016/j.ccell.2015.08.004