The phase 3 RATIONALE 302 trial demonstrated that compared to chemotherapy, tislelizumab showed a statistically significant and clinically meaningful improvement in overall survival in the intention-to-treat population of patients with advanced or metastatic esophageal squamous cell carcinoma.
The global, phase 3 RATIONALE 302 trial (NCT03430843) of the anti–PD-1 antibody tislelizumab (BGB-A317) compared with investigator’s choice of chemotherapy met its primary end point of overall survival (OS) superiority in patients with advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC) who have received prior systemic treatment, according to the agent’s developer, BeiGene.
Tislelizumab is a humanized IgG4 anti–-PD-1 monoclonal antibody designed to reduce binding to FcγR on macrophages. Specifically, when compared with chemotherapy, tislelizumab demonstrated a statistically significant and clinically meaningful improvement in OS in the intention-to-treat (ITT) population of patients.
Notably, the safety profile of tislelizumab was also found to be consistent with its known risks, and no new safety signals were identified.
“Esophageal cancer represents a significant unmet medical need with rapid progression and high mortality. Recent years have seen a paradigm shift in advanced ESCC treatment from chemotherapy and radiation to immunotherapy,” lead investigator Lin Shen, MD, vice president of Clinical Oncology at Beijing Cancer Hospital, said in a press release. “The positive topline results from the RATIONALE 302 trial demonstrated that tislelizumab may offer a new treatment option for those living with this devastating disease and bring hope to patients and their families.”
The randomized, open-label, multicenter trial enrolled a total of 512 patients from 11 countries across Asia, Europe, and North America. Participants were randomized 1:1 to receive either tislelizumab or the investigator’s choice of paclitaxel, docetaxel, or irinotecan.
BeiGene indicated it intends to discuss the RATIONALE 302 data with health authorities globally and present data from the trial at an upcoming medical conference.
Tislelizumab has already been granted full approval by the China National Medical Products Administration (NMPA) for first-line treatment of patients with advanced squamous non–-small cell lung cancer (NSCLC) in combination with chemotherapy. Moreover, tislelizumab has also received conditional approval from the NMPA for the treatment of patients with classical Hodgkin’s lymphoma who received at least 2 prior therapies and for the treatment of patients with locally advanced or metastatic urothelial carcinoma with high PD-L1 expression whose disease progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. However, full approval for these indications remains dependent upon results from ongoing, randomized, controlled confirmatory trials. Tislelizumab is not currently approved for use outside of China.
Two supplemental new drug applications for tislelizumab have been accepted by the Center for Drug Evaluation of the NMPA and are currently under review for first-line treatment of patients with advanced nonsquamous NSCLC in combination with chemotherapy, and for patients with previously treated unresectable hepatocellular carcinoma.
Thirteen phase 3 and 2 pivotal phase 2 trials are ongoing in China and globally.
BeiGene announces positive topline results for global phase 3 trial of tislelizumab in esophageal squamous cell carcinoma. News release. BeiGene. Published January 27, 2021. Accessed January 27, 2021. https://ir.beigene.com/news-releases/news-release-details/beigene-announces-positive-topline-results-global-phase-3-trial?loc=us