The Food and Drug Administration (FDA) has accepted for review the Biologics License Application (BLA) for tislelizumab for the treatment of patients with unresectable recurrent locally advanced or metastatic esophageal squamous cell carcinoma after prior systemic therapy.

Tislelizumab is a humanized immunoglobulin G4 (IgG4) monoclonal antibody that blocks programmed cell death protein 1 (PD-1). The investigational drug is designed to minimize the binding to FcγR on macrophages.

The application is supported by data from the randomized, open-label, global phase 3 RATIONALE 302 trial ( Identifier: NCT03430843), which evaluated the efficacy and safety of tislelizumab in 512 adults with advanced or metastatic esophageal squamous cell carcinoma that had progressed during or after first line therapy.

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Patients were randomly assigned 1:1 to receive either tislelizumab intravenously every 3 weeks or the investigator’s choice chemotherapy (paclitaxel, docetaxel, or irinotecan) until disease progression, unacceptable toxicity, or withdrawal. The primary endpoint was overall survival (OS).

Results showed that treatment with tislelizumab met the primary endpoint demonstrating a 30% reduction in the risk of death compared with chemotherapy (hazard ratio [HR] 0.70; 95% I, 0.57-0.85; P =.0001). Median OS was 8.6 months for the tislelizumab arm and 6.3 months for the chemotherapy arm.

Among PD-L1 positive patients (n=157; combined positive score [CPS] ≥10), tislelizumab was associated with significant improvement in OS compared with chemotherapy (HR 0.54; 95% CI, 0.36-0.79; P =.0006); median OS was 10.3 months for the tislelizumab arm and 6.8 months for the chemotherapy arm.

As for safety, fewer patients in the tislelizumab arm discontinued treatment due to a treatment-emergent adverse event.

“We are advancing tislelizumab as a key cornerstone of our immunotherapy program and PD-1 backbone for combination therapy,” said Jeff Legos, Executive Vice President, Global Head of Oncology & Hematology Development, Novartis. “We will work with regulatory authorities to ensure it is available for people with esophageal cancer as soon as possible.”

The BLA was filed in the US by BeiGene on behalf of Novartis. A Prescription Drug User Fee Act target date of July 12, 2022 has been set for the application.


  1. BeiGene announces U.S. FDA acceptance of Biologics License Application for tislelizumab in esophageal squamous cell carcinoma. News release. BeiGene, Ltd. Accessed September 13, 2021.
  2. Novartis announces first FDA filing acceptance for anti-PD-1 antibody tislelizumab for people with esophageal cancer. News release. Novartis. Accessed September 13, 2021.
  3. Shen L, Kato K, Kim SB, et al. RATIONALE 302: Randomized, phase 3 study of tislelizumab versus chemotherapy as second-line treatment for advanced unresectable/metastatic esophageal squamous cell carcinoma. J Clin Oncol. Published online May 28, 2021. doi: 10.1200/JCO.2021.39.15_suppl.4012

This article originally appeared on MPR