What Is Tislelizumab (Tevimbra)? FDA Approval, Licensing and Reimbursement in Turkey

• FDA Approval: Yes (First approval: March 14, 2024 – advanced/metastatic esophageal squamous cell carcinoma)
• Brand Name: Tevimbra
• Active Ingredient: Tislelizumab-jsgr
• Administration: Intravenous infusion (through a vein)
• Class: Anti-PD-1 monoclonal antibody (immune checkpoint inhibitor)
• Category: Immunotherapy / Oncology
• Manufacturer: BeiGene (collaborating with Novartis in some regions)
• Availability in Turkey: Not yet licensed in Turkey. 
• Approved Cancers: Advanced/metastatic esophageal squamous cell carcinoma, First-line gastric carcinoma and gastroesophageal junction cancers

What Is Tislelizumab? How Does It Work?

Tevimbra is an immunotherapy drug used to strengthen the immune response against cancer cells. Its active ingredient, tislelizumab, is a human monoclonal antibody belonging to the immune checkpoint inhibitor class. It was developed particularly for advanced or metastatic solid tumors.

Mechanism of Action

Tislelizumab binds to PD-1 (Programmed Death-1), a protein on immune T cells. Normally, cancer cells activate PD-1 through surface ligands PD-L1 or PD-L2, preventing T cells from attacking them. By blocking this interaction, tislelizumab disables the T-cell “stop” signal, enabling immune cells to recognize and destroy tumor cells again.

This prevents cancer cells from proliferating unnoticed by the immune system and makes the body's natural defenses more effective against the tumor.

FDA (US Food and Drug Administration) Approval History

• March 4, 2025: Tevimbra was approved in the USA with chemotherapy for first-line treatment of advanced esophageal squamous cell carcinoma.
• December 27, 2024: Tevimbra was approved in the USA with chemotherapy for first-line treatment of gastric and gastroesophageal junction cancers.
• March 14, 2024: The FDA approved Tevimbra (tislelizumab-jsgr) for advanced or metastatic esophageal squamous cell carcinoma.
• February 27, 2024: BeiGene's biologics license application for Tevimbra (tislelizumab) in first-line gastric or gastroesophageal junction cancer was accepted by the FDA.
• September 10, 2022: Novartis announced that tislelizumab demonstrated efficacy and tolerability in advanced liver cancer in a Phase III study.
• June 4, 2021: Novartis' investigational checkpoint inhibitor tislelizumab met the primary overall survival endpoint in a pivotal Phase III study following systemic therapy for esophageal cancer.
• May 29, 2020: BeiGene presented Phase 3 data on tislelizumab combined with chemotherapy for advanced squamous non-small cell lung cancer at the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program.
• January 21, 2020: BeiGene announced that the Phase 3 trial of anti-PD-1 antibody tislelizumab in first-line squamous non-small cell lung cancer met its primary progression-free survival endpoint at interim analysis.

Licensing in Turkey

Tevimbra (tislelizumab) currently has no license issued by the Turkish Medicines and Medical Devices Agency (TİTCK) under the Ministry of Health.

Resistance Mechanisms

Tislelizumab is an anti-PD-1 antibody, so its effect depends on enabling immune cells to recognize and destroy tumors. Some tumors or patients, however, may develop mechanisms reducing this effect over time:

• Loss or alteration of PD-L1/PD-L2 expression: Tumor cells may reduce these surface proteins, preventing immune recognition.
• Alternative immune escape pathways: The tumor microenvironment may produce other suppressive molecules (e.g., CTLA-4, LAG-3, TIM-3), silencing the immune response.
• Increased immunosuppressive cells (Treg, MDSC) within the tumor: Reduces immune cell activity.
• Off-target genetic mutations: Tumor cells may develop genetic changes preventing immune recognition.

Absorption

• Tislelizumab is given intravenously, so there is no intestinal absorption in the conventional sense.
• Bioavailability is 100% because it is delivered directly into the bloodstream.

Distribution

• Like a typical IgG4 monoclonal antibody, tislelizumab distributes into intravascular and extravascular fluids.
• Distribution volume is low (reported at approximately 5-8 L) because it remains mainly in blood vessels and lymphatic tissues.

Metabolism

• Unlike small-molecule drugs, tislelizumab is not metabolized through liver enzymes such as CYP450.
• Like other antibodies, it is broken down into amino acids through intracellular lysosomal pathways.

Elimination

• After metabolism, antibody fragments are eliminated through the kidneys or reticuloendothelial system.
• Mean elimination half-life is approximately 10-17 days (varying with dose, patient factors and treatment duration).

Dosing Interval

• Tislelizumab is generally used at 200 mg, or 300 mg for the tislelizumab-jsgr form.
• It is given by intravenous infusion, generally every 3 weeks.
• The initial dose is usually infused over 60 minutes; if well tolerated, subsequent doses may be faster (e.g., 30-60 min).

Esophageal Squamous Cell Carcinoma: Tevimbra, combined with platinum-containing chemotherapy, is indicated as first-line treatment in adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors are PD-L1-positive (≥1). In this setting, tislelizumab is generally combined with platinum-based (e.g., cisplatin or carboplatin) and fluoropyrimidine-based (e.g., 5-FU) chemotherapy. The aim is to reduce tumor burden and strengthen immune responses. It may also be used alone in some patients, particularly those previously treated with another systemic therapy whose disease has progressed.

Gastric and Gastroesophageal Junction Cancers: Tevimbra is also used as first-line treatment for gastric or gastroesophageal junction cancer. It is generally combined with platinum (cisplatin, oxaliplatin) and fluoropyrimidine (5-FU, capecitabine) chemotherapy. The aim is to increase the immune system's ability to recognize and neutralize tumor cells and support chemotherapy-induced tumor shrinkage.

Drug Interactions

• Low risk of conventional drug interactions: Tislelizumab is not metabolized through hepatic CYP450 enzymes like small-molecule drugs. Significant pharmacokinetic interactions with typical enzyme inducers or inhibitors (e.g., rifampicin, ketoconazole) are therefore not expected.
• Caution with Other Immune-Acting Treatments: Tislelizumab works by activating the immune system. Concurrent potent immunosuppressants (e.g., high-dose corticosteroids or immunosuppressive drugs) may therefore reduce efficacy. Corticosteroids may be used briefly in emergencies to manage adverse effects (e.g., immune-mediated toxicity), but prolonged use is not recommended.
• Combination with Other Immunotherapies: In some situations, tislelizumab is combined with anti-VEGF agents (e.g., bevacizumab) or chemotherapy. These combinations may enhance immune responses pharmacodynamically or alter adverse effect risk. Combination protocols therefore require specific medical planning.
• Vaccine Interactions: Live vaccines are not recommended during tislelizumab treatment. Because the immune system is activated, live vaccines may carry a risk of serious infection. Inactivated vaccines may be administered on medical advice.

Precautions

• Immune-Related Adverse Effects: Because tislelizumab activates immunity, immune-mediated adverse effects may be common. Immune responses can cause inflammation in the lungs (pneumonitis), liver (hepatitis), intestines (colitis), thyroid (hypo- or hyperthyroidism) or other endocrine glands (hypophysitis). These conditions are generally controlled with corticosteroids or immunosuppressants, but early diagnosis and intervention are essential.
• Infusion Reactions: Rarely, intravenous infusion may cause allergic reactions, chills, fever, headache or rash. Patients are therefore monitored carefully during the first infusion. Premedication (e.g., antihistamines or corticosteroids) may be given if necessary.
• Infection Risk: Although not directly immunosuppressive, tislelizumab alters immune function and may predispose to atypical infections. Active infections during treatment therefore require medical oversight. Treatment may be stopped for serious infection.
• Liver and Kidney Function: Elevated liver enzymes (AST, ALT) or abnormal kidney function tests may occur. Regular blood tests should therefore monitor liver and kidney function.
• History of Autoimmune Disease: Use tislelizumab cautiously in severe active autoimmune disease (e.g., lupus, rheumatoid arthritis). Because immunity is already overactive, treatment may trigger new flares.
• Vaccinations: Live vaccines are not recommended during treatment. Inactivated vaccines may be administered with medical approval. Influenza or pneumonia vaccines planned during treatment are generally inactivated and therefore safe.
• Pregnancy and Breastfeeding:  Tislelizumab's safety during pregnancy has not been established. Those planning pregnancy should use effective contraception during treatment and for a specified period afterward. Use is also not recommended during breastfeeding.

Adverse Effects

• Fatigue (25–35%)
• Loss of appetite (20–30%)
• Itching (15–25%)
• Rash (10–20%)
• Thyroid dysfunction (hypothyroidism or hyperthyroidism) (10–15%)
• Elevated liver enzymes (AST/ALT increase) (10–20%)
• Diarrhea (10–15%)
• Nausea (10–15%)
• Muscle-joint pain (10–15%)
• Pneumonitis (lung inflammation) (3–5%)
• Colitis (intestinal inflammation) (2–4%)
• Hepatitis (2–4%)
• Endocrine inflammation (e.g., hypophysitis, adrenal insufficiency) (1–3%)
• Infusion-related reactions (1–2%)