Phase 3 RATIONALE 303 Meets Primary End Point of OS in NSCLC

The phase 3 RATIONALE 303 trial met its primary end point of overall survival (OS) in the intention-to-treat (ITT) patient population at the planned interim analysis, as recommended by an independent Data Monitoring Committee (DMC), according to BeiGene, the developer of tislelizumab.

The randomized, open-label, multicenter, global clinical trial is designed to evaluate the efficacy and safety of tislelizumab (BGB-A317) compared to docetaxel (Taxotere) in the second- or third-line setting in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who have progressed on a prior platinum-based chemotherapy.

The primary end point of the trial is OS in all patients (the ITT population) and in patients with high PD-L1 expression. Key secondary end points include objective response rate, duration of response, progression-free survival, and safety.

Overall, 805 patients across 10 countries were randomized 2:1 to either the tislelizumab arm or the docetaxel arm.

“The RATIONALE 303 trial is the third phase 3 trial of tislelizumab in NSCLC that has achieved a positive outcome at interim analysis, and more importantly, marks the first global pivotal trial with a positive outcome in the tislelizumab clinical program, demonstrating BeiGene’s capabilities in global clinical development,” Yong (Ben) Ben, MD, chief medical officer of immuno-oncology at BeiGene, said in a press release. “We look forward to sharing the full results at an upcoming medical conference and providing additional updates on our lung cancer program in the future.”

“As we continue to advance tislelizumab in its broad clinical program, which targets a wide range of prevalent cancer types, we expect to see a growing body of clinical evidence that we believe will help further evaluate this potentially differentiated checkpoint inhibitor and support potential regulatory filings in China and globally,” Ben added.

Importantly, the safety profile of tislelizumab was also found to be consistent with the known risks of tislelizumab, and no new safety signals were identified.

Currently, tislelizumab is approved by the China National Medical Products Administration (NMPA) as a treatment for patients with classical Hodgkin’s lymphoma who received at least 2 prior therapies and for patients with locally advanced or metastatic urothelial carcinoma with PD-L1 high expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. However, Tislelizumab is not approved for use outside of China.

Additionally, 3 supplemental new drug applications for tislelizumab have been accepted by the Center for Drug Evaluation (CDE) of the NMPA and are under review, including for first-line treatment of patients with advanced squamous non-small cell lung cancer (NSCLC) in combination with chemotherapy, for first-line treatment of patients with advanced non-squamous NSCLC in combination with chemotherapy, and for previously treated unresectable hepatocellular carcinoma.

Notably, 16 potentially registration-enabling clinical trials of tislelizumab are also being conducted in China and globally, including 12 phase 3 trials and 4 pivotal phase 2 trials.

Reference:

BeiGene Announces that RATIONALE 303 Trial of Tislelizumab in Non-Small Cell Lung Cancer Met the Primary Endpoint of Overall Survival at Interim Analysis [news release]. Cambridge, Massachusetts & Beijing, China. Published November 17, 2020. Accessed November 17, 2020. https://ir.beigene.com/news-releases/news-release-details/beigene-announces-rationale-303-trial-tislelizumab-non-small?loc=US