On October 17, 2023 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global biotechnology company, reported 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 (Press release, BeiGene, OCT 17, 2023, View Source [SID1234636055]). 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) (Free ESMO Whitepaper) Congress 2023 (Abstract #LBA58).

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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: View Source

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.