NEW YORK – BeiGene on Wednesday said the European Commission approved the anti-PD-1 monoclonal antibody Tevimbra (tislelizumab) with chemotherapy as a first-line treatment for esophageal squamous cell carcinoma (ESCC) and gastric or gastroesophageal junction (G/GEJ) adenocarcinoma.
Tevimbra is already approved as a monotherapy in the EU for patients with unresectable, locally advanced or metastatic ESCC after prior platinum-based chemotherapy and for some non-small cell lung cancer indications in first- and second-line settings.
In ESCC, the EC expanded Tevimbra's previous indication to include first-line treatment with platinum-based chemotherapy in patients with unresectable, locally advanced or metastatic cancer whose tumors express PD-L1 with a tumor area positivity (TAP) score of 5 percent or more. In G/GEJ adenocarcinoma, the commission approved Tevimbra with platinum- and fluoropyrimidine-based chemotherapy for first-line treatment of patients with HER2-negative locally advanced unresectable or metastatic cancer whose tumors express PD-L1 with a TAP score of 5 percent or more.
The commission based its decision on data from the Phase III RATIONALE-305 and RATIONALE-306 trials, in which BeiGene evaluated Tevimbra and chemotherapy in the two advanced cancer settings.
In RATIONALE-305, BeiGene found that patients with unresectable or metastatic G/GEJ cancer treated with Tevimbra and chemo had a median overall survival of 15 months, compared to 12.9 months for those on placebo and chemo. Among those with a PD-L1 TAP score of 5 percent or more, the Tevimbra group lived a median 16.4 months, compared to 12.8 months in the placebo and chemo group.
In RATIONALE-306, the firm enrolled more than 600 patients with unresectable, locally advanced recurrent or metastatic ESCC and found that patients treated with first-line Tevimbra plus chemo had a median overall survival of 17.2 months versus 10.6 months on placebo plus chemo. At three years, among patients with a PD-L1 TAP score of 5 percent or more, the median overall survival was 19.1 months with Tevimbra-chemo, compared to 10 months in the comparator arm.
"Patients diagnosed with advanced gastric and esophageal cancers confront median survival times measured in months, not years — highlighting the urgent need for more effective treatment options," Florian Lordick, director and professor of oncology at the University Cancer Center Leipzig in Germany, said in a statement. "The compelling data from RATIONALE-305 and -306 trials underscore the unique clinical profile of [Tevimbra] and its potential to deliver meaningful improvements in outcomes for eligible patients, offering new hope where it's needed most."
BeiGene has also submitted applications seeking approval of Tevimbra in G/GEJ and esophageal cancer settings in the US. The US Food and Drug Administration's Oncologic Drugs Advisory Committee met in September to consider 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 tumors. The majority of experts in the committee voted that the available data did not support the first-line use of these immunotherapies when combined with chemo in gastric and esophageal cancer patients whose tumors have low or no PD-L1 expression.