BeiGene Announces the Phase 3 RATIONALE 315 Trial Met Primary Endpoints of Major Pathological Response Rate and Event-Free Survival for Tislelizumab Plus Chemotherapy in Patients with Resectable Non-Small Cell Lung Cancer (NSCLC)

• Late-breaking ESMO data show 56.2% of patients with resectable NSCLC who received tislelizumab plus chemotherapy before surgery achieved major pathological response, versus 15.0% of those treated with neoadjuvant chemotherapy alone
• Analysis also found 40.7% of patients on the tislelizumab-based regimen achieved the key secondary endpoint of pathological complete response, compared to 5.7% of patients who received neoadjuvant chemotherapy alone
• In a subsequent interim analysis from RATIONALE 315, addition of tislelizumab to neoadjuvant platinum-based chemotherapy followed by adjuvant tislelizumab monotherapy demonstrated statistically significant improvement in event-free survival compared to neoadjuvant chemotherapy alone

BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, today announced that the Phase 3 RATIONALE 315 study met its dual primary endpoints of major pathological response (MPR) by Blinded Independent Pathology Review (BIPR) and event-free survival (EFS) by Blinded Independent Central Review (BICR), demonstrating statistically significant and clinically meaningful improvements in patients with resectable Stage II or IIIA NSCLC treated with tislelizumab in combination with chemotherapy before surgery and as a single agent after surgery versus neoadjuvant chemotherapy plus placebo followed by placebo after surgery. The tislelizumab plus chemotherapy regimen also showed a statistically significant improvement in pathological complete response (pCR), the key secondary endpoint, after neoadjuvant therapy versus chemotherapy. The MPR and pCR data will be featured as a late-breaking mini oral presentation on October 23 at 2:55 p.m. CEST at the European Society for Medical Oncology (ESMO) Congress 2023 (Abstract #LBA58).

In the study, 56.2% of NSCLC patients treated with tislelizumab in combination with chemotherapy before surgery achieved MPR, compared to 15.0% of patients treated with chemotherapy alone (difference: 41.1%; 95% CI: 33.2-49.1, p<0.0001). MPR is defined as less than 10% residual viable tumor after neoadjuvant therapy. Additionally, 40.7% of patients on the tislelizumab-based regimen achieved pCR, defined as no viable residual tumor after neoadjuvant therapy, compared to 5.7% of patients treated with chemotherapy alone (difference: 35.0%; 95% CI: 27.9-42.1, p<0.0001). Tislelizumab plus chemotherapy was generally well tolerated, with no new safety signals identified.

Additionally, at a recent prespecified interim analysis conducted by the independent data monitoring committee (IDMC), the tislelizumab-based regimen demonstrated a statistically significant improvement in EFS per assessment by BICR. Detailed results will be submitted for presentation at an upcoming medical conference.

"Lung cancer remains the most common type of cancer and the leading cause of cancer-related death worldwide. Despite available treatment options, rates of recurrence within five years remain unacceptably high, underscoring the need for innovative new neoadjuvant and adjuvant interventions to help improve patient outcomes,” said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. “The data from RATIONALE 315 are encouraging and demonstrate that early integration of tislelizumab into the treatment paradigm may help both improve responses at the time of surgery and reduce the recurrence risk for these patients. These results add to the growing evidence suggesting the potential benefits of tislelizumab in treating patients with NSCLC.”

About RATIONALE 315 (NCT04379635)

RATIONALE 315 is a randomized, double-blind, placebo-controlled, Phase 3 trial evaluating the efficacy and safety of neoadjuvant tislelizumab plus platinum-based doublet chemotherapy, followed by surgery and subsequent adjuvant tislelizumab, compared to placebo plus neoadjuvant platinum-based doublet chemotherapy followed by surgery and subsequent adjuvant placebo in patients with resectable Stage II or IIIA NSCLC. The primary endpoints are MPR rate by BIPR and EFS by BICR. The key secondary endpoint is pCR. Other secondary endpoints included overall survival (OS), objective response rate (ORR), disease-free survival (DFS) as assessed by BICR, and investigator assessed EFS. A total of 453 patients were enrolled and randomized 1:1 to receive either tislelizumab or placebo in combination with chemotherapy.

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.^i,ii,iii,iv

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 benefits of tislelizumab in treating patients with NSCLC; 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.

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