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 .

BeiGene, Ltd. announced results from a planned interim analysis of the Phase III RATIONALE 303 trial of its anti-PD-1 antibody tislelizumab compared to docetaxel as second- or third-line therapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in an oral presentation at the American Association for Cancer Research (AACR) Annual Meeting 2021 A supplemental biologics application (sBLA) based on these results from the RATIONALE 303 trial was accepted in March 2021 and is currently under regulatory review in China. Interim Analysis Results from Phase III 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 III 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 Asia, Europe, the Americas, and Oceania were enrolled in the trial. Patients were randomized 2:1 to either the tislelizumab arm or the docetaxel arm. A pre-specified OS interim analysis in the ITT patient population was performed at the data cutoff as of August 10, 2020, and evaluated by the independent data monitoring committee. In the interim analysis, RATIONALE 303 achieved the primary endpoint of OS in the ITT population. Key efficacy results included : i. 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]); ii. 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]); iii. 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]); iv. the pfs rate at 12 months was 23.3% in the tislelizumab arm, compared to 5.7% in the docetaxel arm; v.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 vi.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 : i.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%); ii. grade, greater than 3 teaes, were reported in 206 patients (38.6%) and 193 patients (74.8%) in the tislelizumab arm and docetaxel arm, respectively; iii. serious teaes were reported in 174 patients (32.6%) and 83 patients (32.2%) in the tislelizumab arm and docetaxel arm, respectively; iv. fifty-six patients (10.5%) and 32 patients (12.4%) discontinued treatment due to teaes in the tislelizumab arm and docetaxel arm, respectively; v.thirty-two patients (6.0%) and 11 patients (4.3%) experienced a fatal teae in the tislelizumab arm and docetaxel arm, respectively; and vi. 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.>