Explore an interactive platform to learn about the clinical profile of TEVIMBRA for adult patients with unresectable or metastatic ESCC. [TBD], our on-demand, virtual rep, is available to help you learn more information about TEVIMBRA, including:

2L, second-line; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group Performance Status; ESCC, esophageal squamous cell carcinoma; ITT, intent-to-treat; IV, intravenous; mDOR, median duration of resonse; ORR, overall response rate; OS, overall survival; PD-1, Programmed death receptor-1; PD-L1, programmed death-ligand 1; PFS, progression-free survival; QW, once per week; Q3W, once every 3 weeks; RECIST, Response Evaluation Criteria in Solid Tumors.

References: 1. TEVIMBRA [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2022. 2. Then EO, Lopez M, Saleem S, et al. Esophageal cancer: an updated surveillance epidemiology and end results database analysis. World J Oncol. 2020;11(2):55-64.

INDICATION

TEVIMBRA is a programmed death receptor-1 (PD-1) blocking antibody indicated 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.

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

TEVIMBRA 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. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1–blocking antibody. 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 PD-1/PD-L1–blocking antibodies. Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1–blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue TEVIMBRA depending on severity. In general, if TEVIMBRA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to grade 1 or less. Upon improvement to grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.

Immune-Mediated Pneumonitis: TEVIMBRA can cause immune-mediated pneumonitis, which can be fatal. 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. Immune-mediated pneumonitis occurred in 3.8% (75/1972) of patients receiving TEVIMBRA, including fatal (0.2%), grade 4 (0.3%), grade 3 (1.4%), and grade 2 (1.7%) adverse reactions. Pneumonitis led to permanent discontinuation of TEVIMBRA in 35 (1.8%) patients and withholding of TEVIMBRA in 27 (1.4%) patients. Systemic corticosteroids were required in all patients with pneumonitis. Immune-mediated pneumonitis resolved in 47% of the 75 patients. Of the 27 patients in whom TEVIMBRA was withheld for pneumonitis, 18 reinitiated TEVIMBRA after symptom improvement; of these, 3 (17%) patients had recurrence of pneumonitis.

Immune-Mediated Colitis: TEVIMBRA can cause immune-mediated colitis, which can be fatal. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1–blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 0.9% (17/1972) of patients receiving TEVIMBRA, including grade 3 (0.4%), and grade 2 (0.5%) adverse reactions. Colitis led to permanent discontinuation of TEVIMBRA in 2 (0.1%) patients and withholding of TEVIMBRA in 10 (0.5%) patients. All 17 patients received systemic corticosteroids. Twelve (71%) of the 17 patients received high-dose systemic corticosteroids. Two (12%) of the 17 patients received immunosuppressive treatment. Immune-mediated colitis resolved in 88% of the 17 patients. Of the 10 patients in whom TEVIMBRA was withheld for colitis, 8 reinitiated TEVIMBRA after symptom improvement; of these, 1 (13%) patient had recurrence of colitis.

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

Immune-Mediated Endocrinopathies

Adrenal Insufficiency:

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

Hypophysitis:

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

Thyroid Disorders:

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

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

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

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

Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis:

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

Immune-Mediated Nephritis with Renal Dysfunction: TEVIMBRA can cause immune-mediated nephritis, which can be fatal. Immune-mediated nephritis with renal dysfunction occurred in 0.4% (7/1972) of patients receiving TEVIMBRA, including grade 4 (0.1%), grade 3 (0.1%), and grade 2 (0.2%) adverse reactions. TEVIMBRA was permanently discontinued in 3 (0.2%) patients and treatment was withheld in 3 (0.2%) patients. All patients received systemic corticosteroids. Nephritis with renal dysfunction resolved in 57% of the 7 patients. Of the 3 patients in whom TEVIMBRA was withheld for nephritis, 2 reinitiated TEVIMBRA after symptom improvement; of these, 1 patient had recurrence of nephritis.

Immune-Mediated Dermatologic Adverse Reactions: TEVIMBRA can cause immune-mediated rash or dermatitis. Serious dermatologic toxicities, such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia and systemic symptoms have occurred with PD-1/PD-L1–blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate nonexfoliative rashes. Withhold or permanently discontinue TEVIMBRA depending on severity.

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

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 TEVIMBRA: myositis, myocarditis, arthritis, polymyalgia rheumatica, and pericarditis. 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. Cardiac/Vascular: vasculitis; Nervous System: meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy; Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. 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; Gastrointestinal: pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis; Musculoskeletal and Connective Tissue: polymyositis, rhabdomyolysis, and associated sequelae, including renal failure; Endocrine: hypoparathyroidism; Other (Hematologic/Immune): hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, and solid organ transplant rejection.

Infusion-Related Reactions

TEVIMBRA can cause severe or life-threatening infusion-related reactions. Infusion-related reactions occurred in 4.2% (83/1972) patients receiving TEVIMBRA, including grade 3 or higher (0.3%) reactions. Monitor patients for signs and symptoms of infusion-related reactions. Slow the rate of infusion for mild (grade 1) and interrupt the infusion for moderate (grade 2) infusion-related reactions. For severe (grade 3) or life-threatening (grade 4) infusion-related reactions, stop infusion and permanently discontinue TEVIMBRA.

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. Transplant-related complications include hyperacute graft-vs-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). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit vs risks of treatment with a PD-1/PD-L1–blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

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

Lactation

Due to 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 TEVIMBRA.

Adverse Reactions

Serious adverse reactions occurred in 41% of patients; the most frequent serious adverse reactions (≥2%) were pneumonia, dysphagia, hemorrhage, pneumonitis (including pneumonitis and immune-mediated pneumonitis), and esophageal obstruction. Fatal adverse reactions occurred in 7% of patients who received TEVIMBRA, including the following, which occurred in more than 1 patient: pneumonia/pneumonitis (5 patients), hemorrhage (3 patients), and death due to an unknown cause (3 patients). Permanent discontinuation of TEVIMBRA due to an adverse reaction occurred in 19% of patients. Adverse reactions that resulted in permanent discontinuation in ≥1% of patients were hemorrhage, pneumonitis (including pneumonitis and immune-mediated pneumonitis), and pneumonia.The most common (≥20%) adverse reactions, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased aspartate aminotransferase, musculoskeletal pain, decreased weight, increased alanine aminotransferase, and cough.

Please see full Prescribing Information, including Medication Guide.