Tislelizumab-jsgr (Monograph)

Brand name: Tevimbra
Drug class: Antineoplastic Agents

Introduction

Tislelizumab-jsgr, a programmed death receptor-1 (PD-1)–blocking antibody, is an antineoplastic agent.¹

Uses for Tislelizumab-jsgr

Tislelizumab-jsgr has the following uses:

Tislelizumab-jsgr is indicated for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.¹

Tislelizumab-jsgr Dosage and Administration

General

Tislelizumab-jsgr is available in the following dosage form(s) and strength(s):

Injection: 100 mg/10 mL (10 mg/mL) solution in a single-dose vial.¹

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

Dilute the commercially available injection concentrate prior to use.¹ See full prescribing information for instructions on preparation of the diluted solution.¹

Recommended dosage is 200 mg as an IV infusion once every 3 weeks until disease progression or unacceptable toxicity.¹ Administer the first infusion over 60 minutes.¹ If tolerated, subsequent infusions may be administered over 30 minutes.¹ See full prescribing information for dosage modification recommendations for adverse reactions.¹

Cautions for Tislelizumab-jsgr

Contraindications

None.¹

Warnings/Precautions

Severe and Fatal Immune-mediated Adverse Reactions

Tislelizumab-jsgr is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.¹ Important immune-mediated adverse reactions listed in the Warnings and Precautions section of the prescribing information may not include all possible severe and fatal immune-mediated reactions.¹

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue.¹ Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody.¹ While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of these drugs.¹

Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies.¹ Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.¹ Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment.¹ In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection.¹ Institute medical management promptly, including specialty consultation as appropriate.¹

Withhold or permanently discontinue tislelizumab-jsgr depending on severity.¹ In general, if interruption or discontinuation of therapy is required, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less.¹ Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month.¹ Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.¹

Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below.¹

Immune-mediated Pneumonitis

Tislelizumab-jsgr can cause immune-mediated pneumonitis, which can be fatal.¹ In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.¹

Immune-mediated pneumonitis occurred in 3.8% (75/1972) of patients receiving tislelizumab-jsgr, including fatal (0.2%), Grade 4 (0.3%), Grade 3 (1.4%), and Grade 2 (1.7%) adverse reactions.¹ Pneumonitis led to permanent discontinuation of tislelizumab-jsgr in 35 (1.8%) patients and withholding of the drug in 27 (1.4%) patients.¹

Systemic corticosteroids were required in all patients with pneumonitis.¹ Immune-mediated pneumonitis resolved in 47% of the 75 patients.¹ Of the 27 patients in whom tislelizumab-jsgr was withheld for pneumonitis, 18 reinitiated the drug after symptom improvement; of these, 3 (17%) patients had recurrence of pneumonitis.¹

Immune-mediated Colitis

Tislelizumab-jsgr can cause immune-mediated colitis, which can be fatal.¹ Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies.¹ In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.¹

Immune-mediated colitis occurred in 0.9% (17/1972) of patients receiving tislelizumab-jsgr, including Grade 3 (0.4%), and Grade 2 (0.5%) adverse reactions.¹ Colitis led to permanent discontinuation of tislelizumab-jsgr in 2 (0.1%) patients and withholding of the drug in 10 (0.5%) patients.¹ All 17 patients received systemic corticosteroids.¹ Twelve (71%) of the 17 patients received high-dose systemic corticosteroids.¹ Two (12%) of the 17 patients received immunosuppressive treatment.¹ Immune-mediated colitis resolved in 88% of the 17 patients.¹ Of the 10 patients in whom tislelizumab-jsgr was withheld for colitis, 8 reinitiated tislelizumab-jsgr after symptom improvement; of these, 1 (13%) patient had recurrence of colitis.¹

Immune-mediated Hepatitis

Tislelizumab-jsgr can cause immune-mediated hepatitis, which can be fatal.¹

Immune-mediated hepatitis occurred in 1.7% (34/1972) of patients receiving tislelizumab-jsgr, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (1%), and Grade 2 (0.6%) adverse reactions.¹ Immune-mediated hepatitis led to permanent discontinuation in 9 (0.5%) patients and withholding of the drug in 20 (1%) patients.¹ All patients received systemic corticosteroids.¹ Twenty-nine (85%) of the 34 patients received high-dose systemic corticosteroids.¹ One patient (2.9%) of the 34 patients received immunosuppressive treatment.¹ Immune-mediated hepatitis resolved in 59% of the 34 patients.¹ Of the 20 patients in whom tislelizumab-jsgr was withheld for hepatitis, 12 reinitiated the drug after symptom improvement; of these, 2 (17%) patients had recurrence of hepatitis.¹

Immune-mediated Endocrinopathies

Tislelizumab-jsgr can cause immune-mediated adrenal insufficiency.¹ For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.¹ Withhold tislelizumab-jsgr depending on severity.¹ Immune-mediated adrenal insufficiency occurred in 0.3% (6/1972) of patients receiving tislelizumab-jsgr, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.2%) adverse reactions.¹ Adrenal insufficiency did not lead to permanent discontinuation of tislelizumab-jsgr.¹ Tislelizumab-jsgr was withheld in 5 out of the 6 patients.¹ All 6 patients received systemic corticosteroids.¹ Two (33%) of the 6 patients received high-dose systemic corticosteroids.¹ Adrenal insufficiency resolved in 17% of the 6 patients.¹

Tislelizumab-jsgr can cause immune-mediated hypophysitis.¹ Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects.¹ Hypophysitis can cause hypopituitarism.¹ Initiate hormone replacement as clinically indicated.¹ Withhold or permanently discontinue tislelizumab-jsgr depending on severity.¹ Hypophysitis/hypopituitarism occurred in 0.1% (1/1972) of patients receiving tislelizumab-jsgr, including a Grade 2 (0.1%) adverse reaction.¹ No treatment discontinuation or withholding of therapy was required.¹

Tislelizumab-jsgr can cause immune-mediated thyroid disorders.¹ Thyroiditis can present with or without endocrinopathy.¹ Hypothyroidism can follow hyperthyroidism.¹ Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.¹ Withhold or permanently discontinue tislelizumab-jsgr depending on severity.¹

Immune-mediated thyroiditis occurred in 0.4% (7/1972) of patients receiving tislelizumab-jsgr, including Grade 2 (0.3%) adverse reactions.¹ Thyroiditis did not lead to permanent discontinuation of therapy.¹ Tislelizumab-jsgr was withheld in 1 (0.1%) patient.¹ One (14%) of the 7 patients received systemic corticosteroids.¹ Thyroiditis resolved in 29% of the 7 patients.¹

Immune-mediated hyperthyroidism occurred in 0.6% (12/1972) of patients receiving tislelizumab-jsgr, including Grade 3 (0.1%), and Grade 2 (0.5%) adverse reactions.¹ Hyperthyroidism led to the permanent discontinuation of tislelizumab-jsgr in 1 (0.1%) patient and withholding of tislelizumab-jsgr in 1 (0.1%) patient.¹ One (8%) of the 12 patients received systemic corticosteroids.¹ Hyperthyroidism resolved in 92% of the 12 patients.¹

Immune-mediated hypothyroidism occurred in 7% (132/1972) of patients receiving tislelizumab-jsgr, including Grade 4 (0.1%) and Grade 2 (5%) adverse reactions.¹ Tislelizumab-jsgr was not permanently discontinued in any patient, while treatment was withheld in 6 (0.3%) patients.¹ Two (1.5%) of the 132 patients received systemic corticosteroids.¹ All 132 patients received hormone replacement therapy.¹ Hypothyroidism resolved in 27% of the 132 patients.¹ The majority (86%) of patients with hypothyroidism required long-term thyroid hormone replacement.¹

Type 1 diabetes mellitus has been reported with PD-1/PD-L1 blocking antibodies.¹ Monitor patients for hyperglycemia or other signs and symptoms of diabetes.¹ Initiate treatment with insulin as clinically indicated.¹ Withhold or permanently discontinue tislelizumab-jsgr depending on severity.¹

Immune-mediated Nephritis with Renal Dysfunction

Tislelizumab-jsgr can cause immune-mediated nephritis, which can be fatal.¹

Immune-mediated nephritis with renal dysfunction occurred in 0.4% (7/1972) of patients receiving tislelizumab-jsgr, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.2%) adverse reactions.¹ Tislelizumab-jsgr was permanently discontinued in 3 (0.2%) patients and treatment was withheld in 3 (0.2%) patients.¹ All patients received systemic corticosteroids.¹ Nephritis with renal dysfunction resolved in 57% of the 7 patients.¹ Of the 3 patients in whom tislelizumab-jsgr was withheld for nephritis, 2 reinitiated therapy after symptom improvement and one patient had recurrence of nephritis.¹

Immune-mediated Dermatologic Adverse Reactions

Tislelizumab-jsgr can cause immune-mediated rash or dermatitis.¹ Cases of severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, some with fatal outcome.¹ Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.¹ Withhold or permanently discontinue tislelizumab-jsgr depending on severity.¹

Immune-mediated dermatologic adverse reactions occurred in 1.2% (24/1972) of patients receiving tislelizumab-jsgr, including Grade 4 (0.2%), Grade 3 (0.4%), and Grade 2 (0.4%) adverse reactions.¹ Dermatologic adverse reactions led to permanent discontinuation of tislelizumab-jsgr in 3 (0.2%) patients and withholding of therapy in 9 (0.5%) patients.¹ Twenty-three (96%) of the 24 patients received systemic corticosteroids.¹ Immune-mediated skin reactions resolved in 58% of the 24 patients.¹ Of the 9 patients in whom tislelizumab-jsgr was withheld for dermatologic adverse reactions, 8 reinitiated the drug after symptom improvement; of these, 2 (25%) patients had recurrence of immune-mediated rash.¹

Other Immune-mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1972 patients who received tislelizumab-jsgr: myositis, myocarditis, arthritis, polymyalgia rheumatica, and pericarditis.¹

The following additional clinically significant immune-mediated adverse reactions have been reported with other PD-1/PD-L1 blocking antibodies, including severe or fatal cases:¹

Cardiac/Vascular: Vasculitis.¹

Nervous System:Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barre syndrome, nerve paresis, autoimmune neuropathy.¹

Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment.¹ Various grades of visual impairment, including blindness, can occur.¹ If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.¹

Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.¹

Musculoskeletal and Connective Tissue: Polymyositis, rhabdomyolysis and associated sequelae including renal failure.¹

Endocrine: Hypoparathyroidism.¹

Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.¹

Infusion-related Reactions

Tislelizumab-jsgr can cause severe or life-threatening infusion-related reactions.¹ Infusion-related reactions occurred in 4.2% (83/1972) patients receiving tislelizumab-jsgr, including Grade 3 or higher (0.3%) reactions.¹ Monitor patients for signs and symptoms of infusion-related reactions.¹

Slow the rate of infusion for mild (Grade 1) and interrupt the infusion for moderate (Grade 2) infusion-related reactions.¹ For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue tislelizumab-jsgr.¹

Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody.¹ Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause).¹ These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.¹

Follow patients closely for evidence of transplant-related complications and intervene promptly.¹ Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.¹

Embryo-fetal Toxicity

Based on its mechanism of action, tislelizumab-jsgr can cause fetal harm when administered to a pregnant woman.¹ 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.¹ Advise women of the potential risk to a fetus.¹ Advise females of reproductive potential to use effective contraception during treatment with tislelizumab-jsgr and for 4 months after the last dose.¹

Specific Populations

Pregnancy

Based on its mechanism of action, tislelizumab-jsgr can cause fetal harm when administered to a pregnant woman.¹ There are no available data on the use of tislelizumab-jsgr in pregnant women.¹ 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.¹ 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.¹ Advise women of the potential risk to a fetus.¹

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.¹

Lactation

There is no information regarding the presence of tislelizumab-jsgr in human milk, or its effects on the breastfed child or on milk production.¹ Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 4 months after the last dose of the drug.¹

Females and Males of Reproductive Potential

Tislelizumab-jsgr can cause fetal harm when administered to a pregnant woman.¹

Verify pregnancy status in females of reproductive potential prior to initiating tislelizumab-jsgr.¹

Advise females of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of the drug.¹

Pediatric Use

The safety and effectiveness of tislelizumab-jsgr have not been established in pediatric patients.¹

Geriatric Use

Of the 256 patients with esophageal squamous cell carcinoma (ESCC) who were treated with tislelizumab-jsgr in the clinical study RATIONALE-302, 39% were 65 years of age and older.¹ No overall differences in safety or effectiveness were observed between elderly patients and younger patients.¹

Common Adverse Effects

Most common adverse reactions (≥20%), including laboratory abnormalities with tislelizumab-jsgr were 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.¹

Related/similar drugs

Keytruda, capecitabine, pembrolizumab, Xeloda, trastuzumab, Herceptin, bleomycin

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

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.¹ 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.¹

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.¹ Tislelizumab-jsgr decreased tumor growth in xenograft models and a human PD-1 transgenic mouse model.¹

Advice to Patients

• Advise patients to read the FDA-approved patient labeling (Medication Guide).¹

• Inform patients of the risk of immune-mediated adverse reactions that may be severe or fatal, may occur after discontinuation of treatment, and may require corticosteroid treatment and interruption or discontinuation of therapy.¹ These reactions may include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic adverse reactions.¹ Other immune-mediated adverse reactions can occur and may involve any organ system; advise patients to contact their healthcare provider immediately for any new or worsening signs or symptoms.¹

• Advise patients to contact their healthcare provider immediately for symptoms of pneumonitis (e.g., new or worsening cough, chest pain, or shortness of breath).¹

• Advise patients to contact their healthcare provider immediately for symptoms of colitis (e.g., diarrhea, severe abdominal pain).¹

• Advise patients to contact their healthcare provider immediately for symptoms of hepatitis (e.g., jaundice, severe nausea or vomiting, pain on the right side of the abdomen, or easy bruising or bleeding).¹

• Advise patients to contact their healthcare provider immediately for signs or symptoms of hypophysitis, adrenal insufficiency, hypothyroidism, hyperthyroidism, thyroiditis, or Type 1 diabetes mellitus.¹

• Advise patients to contact their healthcare provider immediately for signs or symptoms of nephritis.¹

• Advise patients to contact their healthcare provider immediately for any signs or symptoms of severe skin reactions, SJS, TEN, or DRESS.¹

• Advise patients of the risk of solid organ transplant rejection and to contact their healthcare provider immediately for signs or symptoms of organ transplant rejection.¹

• Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions.¹

• Advise patients of potential risk of post-allogeneic hematopoietic stem cell transplantation complications.¹

• Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy.¹ Advise females of reproductive potential to use effective contraception during treatment with tislelizumab-jsgr and for 4 months after the last dose.¹

• Advise women not to breastfeed during treatment with tislelizumab-jsgr and for 4 months after the last dose.¹

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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