BeiGene Presents Interim Analysis Results of RATIONALE 303 Trial of Tislelizumab in Second- or Third-Line Non-Small Cell Lung Cancer at the AACR Annual Meeting 2021
Apr 12, 2021 1:30 PM
- The global Phase 3 trial achieved its primary endpoint, with tislelizumab significantly prolonging overall survival in all patients, regardless of PD-L1 status;
- Tislelizumab was generally well-tolerated, consistent with known risks;
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A supplemental biologics license application for tislelizumab in this indication was accepted for review in
China inMarch 2021 .
“Tislelizumab continues to demonstrate its potential in delivering meaningful survival benefit to patients with advanced or metastatic NSCLC in both the second- and third-line setting, as shown in today’s reported results, as well as with treatment-naïve populations as previously reported at last year’s ASCO and ESMO meetings,” commented
Interim Analysis Results from Phase 3 RATIONALE 303 Trial of Tislelizumab vs. Docetaxel in Second- or Third-Line Locally Advanced or Metastatic NSCLC
Presentation Number: CT039
RATIONALE 303 is a randomized, open-label, multicenter global Phase 3 trial (NCT03358875) designed to evaluate the efficacy and safety of tislelizumab compared to docetaxel in the second- or third-line setting in patients with locally advanced or metastatic NSCLC who have progressed on prior platinum-based chemotherapy. The dual primary endpoints of the trial are overall survival (OS) in intent-to-treat (ITT) patients and OS in patients with high PD-L1 expression; key secondary endpoints include objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), and safety. A total of 805 patients in 10 countries across
“Based on the RATIONALE 303 trial results, compared to docetaxel standard of care, tislelizumab significantly prolonged the median OS by more than five months in all patients and was able to yield a consistent OS benefit across all patients, regardless of PD-L1 status,” said Caicun Zhou, M.D., Ph.D., Director of the
A pre-specified OS interim analysis in the ITT patient population was performed at the data cutoff as of
In the interim analysis, RATIONALE 303 achieved the primary endpoint of OS in the ITT population. Key efficacy results included:
- In the ITT population, the median OS was 17.2 months (95% CI: 15.28, 20.04) in the tislelizumab arm, a significant improvement compared to 11.9 months (95% CI: 10.18, 13.93) in the docetaxel arm (p <0.0001; hazard ratio [HR]=0.64 [95% CI: 0.527, 0.778]);
- In the PD-L1 high population, the median OS was 19.1 months (95% CI: 16.82, 25.79), a significant improvement compared to 11.9 months (95% CI: 8.90, 14.03) in the docetaxel arm (descriptive p <0.0001; HR = 0.52 [95% CI: 0.384, 0.713]);
- The median PFS in the tislelizumab arm was 4.1 months (95% CI: 3.75, 5.03), compared to 2.6 months (95% CI: 2.17, 3.78) in the docetaxel arm (descriptive p <0.0001; HR = 0.64 [95% CI: 0.533, 0.758]);
- The PFS rate at 12 months was 23.3% in the tislelizumab arm, compared to 5.7% in the docetaxel arm;
- The ORR in the tislelizumab arm was 21.9%, compared to 7.0% in the docetaxel arm, with a difference of 14.9% (95% CI: 10.26, 19.56; descriptive p <0.0001); and
- The median DoR in the tislelizumab arm and the docetaxel arm was 13.5 months (95% CI: 8.54, 21.78) and 6.2 months (95% CI: 2.10, 7.16), respectively.
In the interim analysis, tislelizumab showed a safety profile consistent with data previously observed in other tislelizumab monotherapy studies as well as other PD-1/L1 inhibitors. Overall safety results included:
- In the tislelizumab arm, 509 patients (95.3%) experienced at least one treatment-emergent adverse event (TEAE) with the most common being anemia (28.5%), increased alanine aminotransferase (ALT; 19.9%), and cough (19.5%), compared to 254 patients (98.4%) in the docetaxel arm with the most common being alopecia (47.3%), anemia (43.4%), and decreased neutrophil count (36.8%);
- Grade ≥3 TEAEs were reported in 206 patients (38.6%) and 193 patients (74.8%) in the tislelizumab arm and docetaxel arm, respectively;
- Serious TEAEs were reported in 174 patients (32.6%) and 83 patients (32.2%) in the tislelizumab arm and docetaxel arm, respectively;
- Fifty-six patients (10.5%) and 32 patients (12.4%) discontinued treatment due to TEAEs in the tislelizumab arm and docetaxel arm, respectively;
- Thirty-two patients (6.0%) and 11 patients (4.3%) experienced a fatal TEAE in the tislelizumab arm and docetaxel arm, respectively; and
- In the tislelizumab arm, hypothyroidism (7.5%) and pneumonitis (2.2%) were the most common immune-mediated TEAEs of any grade and of Grade ≥3, respectively.
About Non-Small Cell
Lung cancer remains the second most common type of cancer and the leading cause of cancer-related death worldwide.i NSCLC accounts for approximately 85% of all lung cancer cases and is usually diagnosed at an advanced stage.ii The five-year survival rate with treatment for stage IIIB and stage IV NSCLC is 5% and 2%, respectively.iii In
About Tislelizumab
Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody 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.
In addition, three supplemental Biologics License Applications for tislelizumab have been accepted by the
Currently, 16 filed or potentially registration-enabling clinical trials are being conducted in
In
Tislelizumab is not approved for use outside of
About the Tislelizumab Clinical Program
Clinical trials of tislelizumab include:
- Phase 3 trial comparing tislelizumab with docetaxel in the second- or third-line setting in patients with NSCLC (NCT03358875);
- Phase 3 trial comparing tislelizumab to salvage chemotherapy in patients with relapsed/refractory classical Hodgkin Lymphoma (NCT04486391);
- Phase 3 trial in patients with locally advanced or metastatic urothelial carcinoma (NCT03967977);
- Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced squamous NSCLC (NCT03594747);
- Phase 3 trial of tislelizumab in combination with chemotherapy versus chemotherapy as first-line treatment for patients with advanced non-squamous NSCLC (NCT03663205);
- Phase 3 trial of tislelizumab in combination with platinum-based doublet chemotherapy as neoadjuvant treatment for patients with NSCLC (NCT04379635);
- Phase 3 trial of tislelizumab combined with platinum and etoposide versus placebo combined with platinum and etoposide in patients with extensive-stage small cell lung cancer (NCT04005716);
- Phase 3 trial comparing tislelizumab with sorafenib as first-line treatment for patients with hepatocellular carcinoma (HCC; NCT03412773);
- Phase 2 trial in patients with previously treated unresectable HCC (NCT03419897);
- Phase 2 trial in patients with locally advanced or metastatic urothelial bladder cancer (NCT04004221);
- Phase 3 trial comparing tislelizumab with chemotherapy as second-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC; NCT03430843);
- Phase 3 trial of tislelizumab in combination with chemotherapy as first-line treatment for patients with ESCC (NCT03783442);
- Phase 3 trial of tislelizumab versus placebo in combination with chemoradiotherapy in patients with localized ESCC (NCT03957590);
- Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment for patients with gastric cancer (NCT03777657);
- Phase 2 trial in patients with MSI-H/dMMR solid tumors (NCT03736889); and
- Phase 3 trial of tislelizumab combined with chemotherapy versus placebo combined with chemotherapy as first-line treatment in patients with nasopharyngeal cancer (NCT03924986).
About
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 data from the RATIONALE-303 trial of tislelizumab compared to docetaxel in the second- or third-line setting in patients with locally advanced or metastatic non-small cell lung cancer who have progressed on prior platinum-based chemotherapy, the filing and potential approval of an sBLA in
i Globocan 2020. https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed
ii
iii U.S.
iv She J, Yang P, Hong Q, et al. Lung cancer in
v Globocan 2020. https://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf. Accessed
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