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BeiGene Presents Updated Results from Phase 3 RATIONALE-309 Trial of PD-1 Inhibitor Tislelizumab in First-Line RM-NPC in Virtual ASCO Plenary Series

Progression-Free Survival Benefit of Tislelizumab in Combination with Chemotherapy Sustained at Median 15.5 Month Follow-up. Secondary Survival Endpoint Findings Were Consistent with Interim Analysis

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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 the presentation of updated data analyses from the Phase 3 RATIONALE-309 trial of tislelizumab, a humanized anti-PD-1 monoclonal antibody, in combination with chemotherapy versus chemotherapy plus placebo as a first-line treatment for patients with recurrent or metastatic nasopharyngeal cancer (RM-NPC), at the virtual American Society of Clinical Oncology (ASCO) Plenary Series on April 19, 2022.

Updated efficacy analyses showed that, at a median follow-up of 15.5 months, tislelizumab in combination with chemotherapy continued to demonstrate a clinically significant progression-free survival (PFS) benefit over chemotherapy alone for patients with RM-NPC. The safety profile of the tislelizumab and chemotherapy combination was generally manageable and consistent with known risks of each treatment agent.

“These updated findings further support tislelizumab in combination with chemotherapy as a potential standard-of-care first-line therapy for patients with RM-NPC,” said Mark Lanasa, Chief Medical Officer, Solid Tumors at BeiGene. “This study’s acceptance for presentation as part of the high-profile virtual ASCO Plenary Series underscores the potential for tislelizumab plus chemotherapy to be a practice-changing option for patients with this disease.”

An updated analysis of the primary endpoint (PFS) and two secondary endpoints (PFS2, OS) was performed based on the latest database cutoff as of Sept. 30, 2021. At a median follow-up of 15.5 months, patients administered a 200 mg dose of tislelizumab in combination with chemotherapy achieved a median PFS of 9.6 months (stratified hazard ratio (HR)=0.50 [CI: 0.37, 0.68]) compared to 7.4 months for patients dosed with placebo control and chemotherapy, as assessed by an independent review committee (IRC).

“In these updated findings from the RATIONALE-309 trial, tislelizumab in combination with chemotherapy continued to demonstrate PFS benefit over chemotherapy in patients with advanced nasopharyngeal carcinoma, while also showing benefit across a range of other survival endpoints,” said Li Zhang, M.D., professor at the Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China and Sun Yat-sen University Cancer Center, and the principal investigator for the study. “These results continue to support the potential for tislelizumab in combination with chemotherapy as a standard-of-care treatment in first-line RM-NPC.”

This trial’s cross over design allows patients from the placebo plus chemotherapy group to receive tislelizumab monotherapy after disease progression. Disease progression or death after next-line therapy (PFS2) was recorded to explore the optimal treatment sequence. For patients treated with tislelizumab plus chemotherapy, median PFS2 was not yet reached compared to 13.9 months for those treated with placebo plus chemotherapy (HR=0.38 [95% CI: 0.25, 0.58]). A positive overall survival (OS) trend was also observed with median OS not yet reached in the tislelizumab combination arm and 23 months for the chemotherapy plus placebo arm (HR=0.60 [95% CI: 0.25, 1.01]).

Biomarker analyses to be presented were performed for exploratory endpoints including PD-L1 and gene expression profiling (GEP). An improvement in PFS for tislelizumab in combination with chemotherapy was observed regardless of PD-L1 status. GEP analysis identified a subgroup of patients who had ‘hot’ tumor immune profiles, which was characterized by the highest expression of immune cells, including T cells, natural killer cells, dendritic cells, and antigen presentation machinery. The greatest PFS benefit of tislelizumab in combination with chemotherapy was observed in patients exhibiting ‘hot’ tumor microenvironment profiles.

In August 2021, the China National Medical Products Administration (NMPA) accepted a supplemental New Drug Application (sNDA) for tislelizumab in combination with chemotherapy as a first-line treatment of adult patients with RM-NPC. BeiGene continues to support planned regulatory filings by Novartis for first-line NPC in the United States and Europe.

ASCO Plenary Series Program
Tuesday, April 19, 2022; 3 – 4 p.m. ET

This livestream event presented by ASCO will feature a presentation of abstract #384950, “RATIONALE-309 Updated progression-free survival (PFS), PFS after next line of treatment, and overall survival from a phase 3 double-blind trial of tislelizumab versus placebo, plus chemotherapy, as first-line treatment for recurrent/metastatic nasopharyngeal cancer” by Dr. Zhang. Participants may register for free at:

About Nasopharyngeal Carcinoma

Nasopharyngeal carcinoma (NPC) is a rare cancer in which malignant cells form in the tissues of the nasopharynx and accounts for approximately 133,000 new diagnoses and 80,000 deaths per year worldwide.1

Recurrent or metastatic NPC exhibits a high prevalence in Southeast Asia, among other emerging markets. Known risk factors include ethnic background exposure to the Epstein-Barr virus. The prognosis for patients with recurrent or metastatic NPC treated with first-line chemotherapy remains poor, highlighting the unmet need for effective interventional therapy in the second line or later.


RATIONALE-309 is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial (NCT03924986) designed to evaluate the efficacy and safety of tislelizumab combined with gemcitabine and cisplatin (Arm A) versus placebo combined with gemcitabine and cisplatin (Arm B) as a first-line treatment for patients with RM-NPC.

The primary endpoint of the trial is progression-free survival (PFS) in the intent-to-treat (ITT) population as assessed by an independent review committee (IRC) per RECIST v1.1 criteria; secondary endpoints include IRC-assessed overall response rate (ORR), IRC-assessed duration of response (DoR), overall survival (OS), investigator-assessed PFS, time to second objective disease progression (PFS2), and safety.

A total of 263 patients were enrolled in the trial, with 131 and 132 randomized to Arm A and Arm B, respectively, with balanced baseline characteristics between both arms. Interim results from the trial were presented in December at the European Society for Medical Oncology Immuno-Oncology (ESMO I-O) Congress. Those data showed that at a media follow-up time of 10 months, tislelizumab demonstrated a statistically significant improvement in terms of extending progression-free survival (PFS), a clinically meaningful benefit compared to chemotherapy alone on other survival endpoints, and a generally manageable safety profile.

About Tislelizumab

Tislelizumab is an anti-programmed death receptor-1 (PD-1) inhibitor designed to help aid the body’s immune cells to detect and fight tumors. Tislelizumab, a humanized monoclonal antibody, is specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR 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.

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.

Tislelizumab is approved by the China National Medical Products Administration (NMPA) as a treatment for eight indications, including multiple approvals in non-small cell lung cancer (NSCLC). Tislelizumab has been submitted for regulatory review in one additional indication in China and as a potential treatment for unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic therapy in the U.S., and in NSCLC and ESCC in Europe. In January 2021, BeiGene partnered with Novartis to accelerate the clinical development and marketing of tislelizumab in the U.S., Europe and Japan.

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