Tislelizumab-Jsgr

FDA Drug Information • Also known as: Tevimbra

Brand Names: Tevimbra
Dosage Form: INJECTION, SOLUTION, CONCENTRATE
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Tislelizumab-jsgr is a programmed death receptor-1 (PD-1)–blocking antibody. Tislelizumab-jsgr is an Fc-engineered humanized monoclonal IgG4 kappa antibody with an approximate molecular weight of 147 kDa. Tislelizumab-jsgr is produced in recombinant Chinese hamster ovary (CHO) cells. TEVIMBRA (tislelizumab-jsgr) injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution for intravenous use, supplied in single-dose vials. Each vial contains 100 mg of tislelizumab-jsgr monoclonal antibody in 10 mL of solution, with a concentration of 10 mg/mL, and is formulated in: citric acid monohydrate (4.2 mg), histidine (17.2 mg), L-histidine hydrochloride monohydrate (8.2 mg), polysorbate 20 (2 mg), sodium citrate (59.3 mg), trehalose (650.4 mg), and Water for Injection, USP. The pH is 6.5.

What Is Tislelizumab-Jsgr Used For?

1 INDICATIONS AND USAGE TEVIMBRA is a programmed death receptor-1 (PD-1)-blocking antibody indicated for: Esophageal Cancer in combination with platinum-containing chemotherapy for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1). ( 1.1 ) as a single agent in adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. ( 1.1 ) Gastric Cancer in combination with platinum and fluoropyrimidine-based chemotherapy in adults for the first line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (≥1). ( 1.2 ) 1.1 Esophageal Cancer First-Line Treatment of Esophageal Squamous Cell Carcinoma TEVIMBRA, in combination with platinum-containing chemotherapy, is indicated for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1). Previously Treated Esophageal Squamous Cell Carcinoma TEVIMBRA, as a single agent, is indicated for the treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor. 1.2 Gastric Cancer TEVIMBRA, in combination with platinum and fluoropyrimidine-based chemotherapy, is indicated for the first-line treatment of adults with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma (G/GEJ) whose tumors express PD-L1 (≥1).

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Recommended Dosage: Esophageal Cancer 150 mg every 2 weeks or 200 mg every 3 weeks or 300 mg every 4 weeks or 400 mg every 6 weeks in combination with platinum-containing chemotherapy for first-line treatment of unresectable or metastatic ESCC. ( 2.2 ) 150 mg every 2 weeks or 200 mg every 3 weeks or 300 mg every 4 weeks or 400 mg every 6 weeks as a single agent for treatment of unresectable or metastatic ESCC. ( 2.2 ) Gastric Cancer 150 mg every 2 weeks or 200 mg every 3 weeks or 300 mg every 4 weeks or 400 mg every 6 weeks in combination with platinum and fluoropyrimidine-based chemotherapy. ( 2.2 ) 2.1 Patient Selection Select patients for the first-line treatment of unresectable or metastatic esophageal squamous cell carcinoma based on the presence of PD-L1 in tumor specimens [see Clinical Studies (14.1) ]. An FDA-approved companion diagnostic for the detection of PD-L1 in patients with unresectable or metastatic esophageal squamous cell carcinoma is not available. Select patients for the first-line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma (G/GEJ) based on the presence of PD-L1 in tumor specimens [see Clinical Studies (14.2) ] . An FDA-approved companion diagnostic for the detection of PD-L1 in patients with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma (G/GEJ) is not available. 2.2 Recommended Dosage The recommended dosages of TEVIMBRA administered intravenously as a single agent or in combination with other therapeutic agents are presented in Table 1. Table 1: Recommended Dosages for TEVIMBRA as a Single Agent or in Combination with Other Therapeutic Agents Indication Recommended Dosage of TEVIMBRA Duration/Timing of Treatment ESCC OR First-Line Gastric Cancer 150 mg every 2 weeks OR 200 mg every 3 weeks OR 300 mg every 4 weeks OR 400 mg every 6 weeks Until disease progression or unacceptable toxicity. Refer to the respective Prescribing Information for each therapeutic agent administered in combination with TEVIMBRA for the recommended dosage information, as appropriate. 2.3 Dosage Modifications for Adverse Reactions No dose reduction of TEVIMBRA is recommended. In general, withhold TEVIMBRA for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue TEVIMBRA for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids [see Warnings and Precautions (5.1) ] . Dosage modifications for TEVIMBRA for adverse reactions that require management different from these general guidelines are summarized in Table 2 . Refer to the respective Prescribing Information for dosage modifications for the platinum and fluoropyrimidine agent administered in...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in more detail in other sections of the label: Severe and fatal immune-mediated adverse reactions [see Warnings and Precautions (5.1) ] Infusion-related reactions [see Warnings and Precautions (5.2) ] Most common adverse reactions (≥20%), including laboratory abnormalities, were: TEVIMBRA in combination with platinum-containing chemotherapy: decreased neutrophil count, decreased sodium, increased glucose, anemia, fatigue, decreased appetite, increased AST, decreased potassium, increased serum creatinine, decreased calcium, increased ALT, diarrhea, stomatitis, and vomiting. ( 6.1 ) TEVIMBRA as a single agent: 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. ( 6.1 ) TEVIMBRA in combination with platinum and fluoropyrimidine-based chemotherapy: nausea, fatigue, decreased appetite, anemia, peripheral sensory neuropathy, vomiting, decreased platelet count, decreased neutrophil count, increased aspartate aminotransferase, diarrhea, abdominal pain, increased alanine aminotransferase, decreased white blood cell count, decreased weight, and pyrexia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact BeOne Medicines at 1-877-828-5596 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in WARNINGS AND PRECAUTIONS reflect exposure to TEVIMBRA as a single agent in 2390 patients enrolled in three randomized open-label, active-controlled studies (BGB-A317-301, RATIONALE-302, BGB-A317-303) and six open-label, single-arm studies (BGB-A317-209, BGB-A317-208, BGB-A317-204, BGB-A317-203, BGB-A317-102, BGB-A317_Study_001), which enrolled 307 patients with esophageal squamous cell carcinoma and 2083 patients with advanced or recurrent tumors. TEVIMBRA was administered at a dose of 200 mg intravenously once every 3 weeks, except in study BGB-A317_Study_001 where patients also received other dosage regimens. Among the 2390 patients, 38% were exposed for longer than 6 months, and 23% were exposed for longer than 12 months. First-line Treatment of Unresectable or Metastatic Esophageal Carcinoma (ESCC) The safety of TEVIMBRA in combination with chemotherapy was evaluated in RATIONALE-306, a randomized, placebo-controlled, multicenter, double-blind trial in patients with unresectable, advanced, or metastatic ESCC [see Clinical Studies (14.1) ] . Patients were randomized (1:1) to receive either TEVIMBRA 200 mg by intravenous infusion over 30-60 minutes every 3 weeks or placebo plus a chemotherapy doublet regimen. The chemotherapy doublet regimens consisted of: Platinum (cisplatin [60 to 80 mg/m 2 IV, on Day 1] or oxaliplatin [130 mg/m 2 IV, on Day 1]) and a fluoropyrimidine (5-FU [750 to 800 mg/m 2 IV, on Day 1 to 5] or capecitabine [1000 mg/m 2 orally twice daily, on Day 1 to 14]) or Platinum (cisplatin [60 to 80 mg/m 2 IV, on Day 1 or 2] or oxaliplatin [130 mg/m 2 IV, on Day 1 or 2]) and (paclitaxel 175 mg/m 2 IV, on Day 1) Patients were treated until disease progression or unacceptable toxicity. The median duration of exposure was 6.4 months (range: 0.1 to 38.3 months) in TEVIMBRA-treated patients. Serious adverse reactions occurred in 48% of patients receiving TEVIMBRA in combination with chemotherapy. The most frequent serious adverse reactions (≥2%) were pneumonia (5.2%), dysphagia (5.2%), diarrhea (2.2%), fatigue (2.2%), and esophageal stenosis (2.2%). Fatal adverse reactions occurred in 8% of patients who received TEVIMBRA in combination with...

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on its mechanism of action, TEVIMBRA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on the use of TEVIMBRA in pregnant women. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death (see Data ) . Human IgG4 immunoglobulins (IgG4) are known to cross the placental barrier; therefore, tislelizumab-jsgr has the potential to be transmitted from the mother to the developing fetus. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Animal reproduction studies have not been conducted with TEVIMBRA to evaluate its effect on reproduction and fetal development. A central function of the PD-1/PD-L1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to the fetus. In murine models of pregnancy, blockade of PD-L1 signaling has been shown to disrupt tolerance to the fetus and to result in an increase in fetal loss; therefore, potential risks of administering TEVIMBRA during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to tislelizumab-jsgr may increase the risk of developing immune-mediated disorders or altering the normal immune response.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied TEVIMBRA injection is a clear to slightly opalescent, colorless to slightly yellow solution supplied in a carton containing one 100 mg/10 mL (10 mg/mL) single-dose vial (NDC 72579-121-01). Storage Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.