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)
Oct 17, 2023 4:01 PM
- 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
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
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.
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,
Tislelizumab is currently under review by the
Regulatory submissions for tislelizumab are also under review by authorities in
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
i Desai J et al. Abstract Book of the 42
ii 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 (
iii 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
iv 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 (
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