Profile
General Information
Tevimbra (tislelizumab-jsgr) is a programmed death receptor-1 (PD-1) blocking antibody.
Tevimbra is specifically indicated as a single agent for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.
Tevimbra is supplied as an injection for intravenous infusion. The recommended dose is 200 mg administered as an intravenous infusion once every 3 weeks, until disease progression or unacceptable toxicity. Administer the first infusion over 60 minutes. If tolerated, subsequent infusions may be administered over 30 minutes.
Mechanism of Action
Tevimbra (tislelizumab-jsgr) is a programmed death receptor-1 (PD-1) blocking antibody. Binding of the PD-1 ligands PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Tislelizumab-jsgr binds to PD-1 and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway mediated inhibition of the immune response, including the anti-tumor immune response. Tislelizumab-jsgr decreased tumor growth in xenograft models and a human PD-1 transgenic mouse model.
Side Effects
Side effects associated with the use of Tevimbra may include, but are not limited to, the following:
- increased glucose
- decreased hemoglobin
- decreased lymphocytes
- decreased sodium
- decreased albumin
- increased alkaline phosphatase
- anemia
- fatigue
- increased AST
- musculoskeletal pain
- decreased weight
- increased ALT
- cough
Clinical Trial Results
The FDA approval of Tevimbra was based on the results of RATIONALE 302 trial. The global, randomized, open-label study was designed to investigate the efficacy and safety of Tevimbra when compared with investigator’s choice of chemotherapy as a second-line treatment for patients with unresectable, locally advanced or metastatic ESCC. The study randomized 512 patients.
The trial met its primary endpoint in the intention-to-treat (ITT) population with a statistically significant and clinically meaningful survival benefit for Tevimbra compared with chemotherapy. In the ITT population, the median overall survival (OS) in the Tevimbra arm was 8.6 months compared to 6.3 months in the chemotherapy arm.