NEW YORK – BeiGene last week said the US Food and Drug Administration approved its anti-PD-1 monoclonal antibody Tevimbra (tislelizumab) with platinum and fluoropyrimidine-based chemotherapy as a first-line treatment for patients with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma tumors that are HER2-negative but have a PD-L1 tumor area positivity (TAP) score of at least 1 percent.
The agency's decision was based on results from the Phase III RATIONALE-305 trial, which showed that patients with a PD-L1 TAP score of at least 1 percent who received Tevimbra and investigator's choice of chemotherapy had a median overall survival of 15 months compared to 12.9 months for patients on placebo plus chemotherapy. Patients on the Tevimbra-chemo combination had a 20 percent reduction in risk of death compared to those who just got chemo.
However, in a small subgroup of 69 patients with PD-L1 TAP scores of less than 1 percent, the median overall survival on Tevimbra-chemo was 15.4 months compared to 13.8 months on chemo alone, with a hazard ratio of nearly 1, indicating no difference in efficacy between the two arms.
In September 2024, the FDA's Oncologic Drugs Advisory Committee considered whether to limit indications for Tevimbra and two other checkpoint inhibitors, Merck's Keytruda (pembrolizumab) and Bristol Myers Squibb's Opdivo (nivolumab), to patients with PD-L1-positive gastric and esophageal cancers. After reviewing the available data, the majority of experts in the committee voted that there wasn't sufficient evidence to support first-line use of these immunotherapies with chemotherapy in tumors with low or no PD-L1 expression.
The European Commission approved Tevimbra-chemo in patients with gastric and esophageal junction cancer whose tumors express PD-L1 with a TAP score of 5 percent or more in November 2024.
Tevimbra is already approved in the US as a monotherapy for patients with unresectable or metastatic esophageal squamous cell carcinoma after systemic chemo, and it is approved for some non-small cell lung cancers in the first- and second-line settings. The FDA is also reviewing another biologics license application from BeiGene seeking Tevimbra's approval in first-line locally advanced, unresectable or metastatic esophageal squamous cell carcinoma.