First-Line Tislelizumab Plus Chemotherapy Approved in ESCC Expressing PD-L1

The FDA today approved tislelizumab (Tevimbra; BeiGene) plus chemotherapy for the first-line treatment of patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1, according to a press release from BeiGene.1

Results from the phase 3 RATIONALE-306 trial supported the FDA approval of tislelizumab plus chemotherapy in the first line. | Image credit: wladimir1804

Tislelizumab was initially approved in 2024 as a second-line monotherapy for unresectable or metastatic ESCC following systemic chemotherapy, and 3-year results from the phase 3 RATIONALE-306 study (NCT03783442) presented at last year's American Society of Clinical Oncology Annual Meeting demonstrated the safety and efficacy of tislelizumab plus chemotherapy in the second line.2

Results from the randomized, placebo-controlled, double-blind RATIONALE-306 also supported the FDA's approval of frontline tislelizumab plus chemotherapy.1 The study met its primary end point, showing a statistically significant improvement in overall survival (OS) in 649 patients randomized to the tislelizumab combination (n = 326) vs a placebo in combination with chemotherapy (n = 323).

The improvement seen in the intent-to-treat population was mostly attributable to the subgroup of patients with PD-L1 greater than or equal to 1 (n = 481), exploratory analyses found. Median OS was 16.8 months in the tislelizumab plus chemotherapy group vs 9.6 months among patients treated with a placebo plus chemotherapy. There was a 34% lower risk of death in the PD-L1 positive subgroup (HR, 0.66; 95% CI, 0.53-0.82).

“The approval of [tislelizumab] in combination with chemotherapy for adult patients with ESCC expands first-line treatment options for patients with this disease,” Nataliya Uboha, MD, PhD, associate professor at the University of Wisconsin, Carbone Cancer Center, said in a statement.1 “There is a critical need for effective treatments of ESCC, and [tislelizumab] has been shown to improve outcomes in this patient population.”

Tislelizumab plus chemotherapy showed a favorable safety profile, with the most frequent serious adverse effects (AEs) affecting at least 2% of patients being pneumonia, dysphagia, diarrhea, fatigue, and esophageal stenosis. The most common AEs impacting at least 20% of patients were anemia, fatigue, decreased appetite, nausea, constipation, decreased weight, diarrhea, peripheral sensory neuropathy, vomiting, and stomatitis.

Tislelizumab is also FDA approved as a monotherapy for ESCC in the second line for patients who were not previously treated with a PD-L1 inhibitor and in combination with platinum and fluoropyrimidine-based chemotherapy as first-line therapy for patients with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1.3

"Today’s approval, our third from the FDA in less than a year, reflects our dedication to advancing innovative therapies and addressing critical needs in cancer care," Mark Lanasa, MD, PhD, chief medical officer, Solid Tumors at BeiGene, said in a statement.1 "FDA approval of [tislelizumab] for the first-line treatment of advanced esophageal squamous cell carcinoma marks a significant step forward in tackling the unmet needs in this challenging disease area. We are grateful to the patients, clinicians, and researchers whose commitment and courage have made this progress possible."

References

1. Tevimbra approved in U.S. for first-line treatment of advanced esophageal squamous cell carcinoma in combination with chemotherapy. News release. BeiGene. March 4, 2025. Accessed March 4, 2025. https://ir.beigene.com/news/tevimbra-approved-in-u-s-for-first-line-treatment-of-advanced-esophageal-squamous-cell-carcinoma-in-combination/8379a7c3-35ce-45af-82d3-164c64ecf37c/

2. Joszt L. Tislelizumab plus chemo meaningfully improves OS, PFS in advanced esophageal cancer. AJMC®. June 14, 2024. Accessed March 4, 2025. https://www.ajmc.com/view/tislelizumab-plus-chemo-meaningfully-improves-os-pfs-in-advanced-esophageal-cancer

3. Tevimbra (tislelizumab-jsgr). Prescribing information. BeiGene;2025. Accessed March 4, 2025. https://www.beigene.com/PDF/TEVIMBRAUSPI.pdf