BeiGene Announces Late-Breaking Data at ESMO Showing Tislelizumab plus Chemotherapy Significantly Improved Overall Survival at Final Analysis in First-Line Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Oct 17, 2023 4:01 PM
- 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
“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
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
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.
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,
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 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
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)."
ii Desai J et al. Abstract Book of the 42
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 (
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 (
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