BeiGene (BGNE) Presents Interim Analysis of Phase 3 Trial of Tislelizumab in NSCLS at AACR

BeiGene, Ltd. (NASDAQ: BGNE) announced results from a planned interim analysis of the Phase 3 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.

“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 Yong (Ben) Ben, M.D., Chief Medical Officer, Immuno-Oncology at BeiGene. “In addition, tislelizumab was generally well-tolerated, consistent with known risks from previously reported results across different tumor types. These encouraging results from RATIONALE 303, which supported the recently accepted sBLA in second- or third-line NSCLC in China, further suggest that tislelizumab is a potentially differentiated checkpoint inhibitor.”

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 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.

“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 Department of Oncology at Shanghai Pulmonary Hospital and Director of Cancer Institute of Tongji University. “Tislelizumab was also tolerated among these patients, with a notably lower incidence rate of Grade ≥3 adverse events compared to docetaxel. We’re encouraged by the promising findings presented today and hope tislelizumab could become an important treatment option for second- or third-line NSCLC patients.”

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:

• 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.

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