On March 14, the U.S. Food and Drug Administration (FDA) approved the humanized immunoglobulin G4 anti–PD-1 monoclonal antibody tislelizumab-jsgr (Tevimbra) as monotherapy for adults with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-1/PD-L1 inhibitor.
RATIONALE 302
The approval is based on the RATIONALE 302 trial (ClinicalTrials.gov identifier NCT03430843), a global, randomized, open-label, phase III study designed to investigate the efficacy and safety of tislelizumab compared with investigator’s choice of chemotherapy as a second-line treatment of unresectable, locally advanced, or metastatic esophageal squamous cell carcinoma. The study randomly assigned 512 patients from 132 research sites in 11 countries in Europe, Asia, and North America.
RATIONALE 302 met its primary endpoint in the intention-to-treat (ITT) population, with a statistically significant and clinically meaningful survival benefit for tislelizumab compared with chemotherapy. In the ITT population, the median overall survival in the tislelizumab arm was 8.6 months (95% confidence interval [CI] = 7.5–10.4 months) compared with 6.3 months (95% CI = 5.3–7.0 months) in the chemotherapy arm (P = .0001; hazard ratio = 0.70, 95% CI = 0.57–0.85).
The safety profile of tislelizumab was also favorable over chemotherapy. The most common (≥ 20%) adverse reactions for patients receiving tislelizumab, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough.
“Patients diagnosed with advanced or metastasized esophageal squamous cell carcinoma, the most common histologic subtype of esophageal cancer, often progress following initial therapy and are in need of new options,” said Syma Iqbal, MD, Associate Professor of Clinical Medicine; Section Chief of Gastrointestinal Oncology, Division of Medical Oncology; and Cancer Physician-in-Chief at the Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California. “The RATIONALE 302 trial showed that patients with previously treated esophageal squamous cell carcinoma who received tislelizumab saw a clinically meaningful survival benefit, highlighting its potential as an important treatment option for these patients.”
The FDA is also reviewing biologics license applications for tislelizumab as a first-line treatment of unresectable, recurrent, locally advanced, or metastatic esophageal squamous cell carcinoma and locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma. The target action dates are July and December 2024, respectively.
