FDA Approves Frontline Tislelizumab/Chemo in Advanced PD-L1+ ESCC

“The approval of [tislelizumab] in combination with chemotherapy for adult patients with ESCC expands first-line treatment options for patients with this disease,” according to Nataliya Uboha, MD, PhD.

The FDA has approved tislelizumab-jsgr (Tevimbra) plus platinum-based chemotherapy as a frontline therapy for adult patients with unresectable or metastatic PD-L1–positive esophageal squamous cell carcinoma (ESCC), according to a press release from the developer, BeiGene.¹

Supporting data for the approval came from the phase 3 RATIONALE-306 trial (NCT03783442) evaluating the tislelizumab-based combination vs chemotherapy plus placebo in 649 adults with unresectable, locally advanced recurrent or metastatic ESCC. Data showed that tislelizumab-based treatment yielded a statistically significant overall survival (OS) improvement, with exploratory analyses indicating that this outcome was primarily attributable to results observed in the PD-L1–positive subgroup (n = 481).

Among patients with PD-L1–positive disease, the median OS was 16.8 months with tislelizumab plus chemotherapy vs 9.6 months with placebo plus chemotherapy. The experimental combination reduced the risk of death by 34% (HR, 0.66; 95% CI, 0.53-0.82).

Safety data from the RATIONALE-306 trial show that the most common serious adverse effects (SAEs) included pneumonia, diarrhea, fatigue, and esophageal stenosis. Additionally, the most common AEs included anemia, fatigue, decreased appetite, nausea, constipation, decreased weight, and diarrhea.

“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, stated in the press release.¹ “There is a critical need for effective treatments of ESCC, and [tislelizumab] has been shown to improve outcomes in this patient population.”

In the double-blind RATIONALE-306 trial, patients were randomly assigned to receive tislelizumab (n = 326) or placebo (n = 323) in combination with chemotherapy.² Patients received tislelizumab at 200 mg intravenously on day 1 of every 3-week cycle or matched placebo in combination with cisplatin or oxaliplatin plus 5-fluorouracil or cisplatin or oxaliplatin plus paclitaxel.

The trial’s primary end point was OS. Secondary end points included progression-free survival, objective response rate, duration of response, health-related quality of life, and AEs.

Patients 18 years and older with pathologically confirmed ESCC and stage IV unresectable disease at first diagnosis or unresectable, locally advanced recurrent or metastatic disease were eligible for enrollment. Those with palliative radiotherapy for ESCC within 4 weeks of study treatment initiation or prior systemic therapy for unresectable, locally advanced recurrent or metastatic disease were ineligible for study entry.

“The FDA approval of [tislelizumab] for the first-line treatment of advanced [ESCC] marks a significant step forward in tackling the unmet needs in this challenging disease area,” Mark Lanasa, MD, PhD, chief medical officer of Solid Tumors at BeiGene, concluded.¹

References

1. TEVIMBRA approved in U.S. for first-line treatment of advanced esophageal squamous cell carcinoma in combination with chemotherapy. News release. BeiGene, Ltd. March 4, 2025. Accessed March 4, 2025. https://tinyurl.com/4np7u39m
2. A study of tislelizumab (BGB-A317) in combination with chemotherapy as first line treatment in participants with advanced esophageal squamous cell carcinoma. ClinicalTrials.gov. Updated October 26, 2024. Accessed March 4, 2025. https://tinyurl.com/yen9mpkx