The Israeli Ministry of Health has approved tislelizumab-jsgr (Tevimbra) as a monotherapy for adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) following prior systemic chemotherapy. This decision brings a new treatment option to patients in Israel facing this aggressive cancer.
The approval is based on the phase 3 RATIONALE 302 trial (NCT03430843), a study that compared tislelizumab to investigator's choice of chemotherapy as a second-line treatment for patients with unresectable, locally advanced, or metastatic ESCC. The results of this trial demonstrated a statistically significant improvement in median overall survival (OS) with tislelizumab compared to chemotherapy.
RATIONALE-302 Trial Results
The RATIONALE-302 trial enrolled 512 patients, with 256 receiving tislelizumab and 256 receiving chemotherapy. The primary endpoint of the study, overall survival (OS) in the intention-to-treat (ITT) population, was met. Patients treated with tislelizumab had a median OS of 8.6 months (95% CI, 7.5-10.4) compared to 6.3 months (95% CI, 5.3-7.0) for those treated with chemotherapy (HR, 0.70; 95% CI, 0.57-0.85; P = .0001). The 12-month OS rates were 37.4% and 23.7% with tislelizumab and chemotherapy, respectively.
Further efficacy results from RATIONALE-302 demonstrated that patients with a PD-L1 tumor area positivity (TAP) score of at least 10% also experienced a statistically significant improvement in median OS with tislelizumab vs chemotherapy, at 10.3 months (95% CI, 8.5-16.1) vs 6.8 months (95% CI, 4.1-8.3), respectively (HR, 0.54; 95% CI, 0.36-0.79; one-sided P = .0006).
Median PFS in the ITT population was 1.6 months (95% CI, 1.4-2.7) with tislelizumab vs 2.1 months (95% CI, 1.5-2.7) with chemotherapy (HR, 0.83; 95% CI, 0.67-1.01). The ORR was 20.3% (95% CI, 15.6%-25.8%) vs 9.8% (95% CI, 6.4%-14.1%) with tislelizumab and chemotherapy, respectively. The median DOR in the tislelizumab and chemotherapy arms was 7.1 months (95% CI, 4.1-11.3) and 4.0 months (95% CI, 2.1-8.2), respectively.
Additional Data and Safety
A prespecified exploratory analysis of the agent’s activity in the European/North American subgroup (n = 108) demonstrated that tislelizumab upheld its OS benefit vs chemotherapy, with a median OS of 11.2 months (95% CI, 5.9-14.8) vs 6.3 months (95% CI, 4.6-7.7), respectively (HR, 0.55; 95% CI, 0.35-0.87). The 12-month OS rates were 42.7% and 17.6% with tislelizumab and chemotherapy, respectively. Similar benefits in OS were seen regardless of PD-L1 TAP score (≥10%: HR, 0.47; 95% CI, 0.18-1.21; <10%: HR, 0.55; 95% CI, 0.30-1.01).
The most common adverse effects that occurred in at least 20% of patients in the tislelizumab arm were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased aspartate aminotransferase, musculoskeletal pain, decreased weight, increased alanine aminotransferase, and cough.
"The recent approval of [tislelizumab] by the Israeli Ministry of Health provides a new, innovative treatment for patients with ESCC, offering renewed hope and potentially improved outcomes for those affected by these challenging malignancies," said Itzik Mizrahi, country general manager of BeiGene Israel, in a news release.
