tecentriq hybreza

Important safety information

Immune-Mediated Adverse Reactions Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, including the following: immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis, immune-mediated endocrinopathies, immune-mediated dermatologic adverse reactions, immune-mediated nephritis and renal dysfunction, and solid organ transplant rejection. ( 5.1 ) Monitor for early identification and management. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. Withhold or permanently discontinue based on severity and type of reaction. Infusion-Related Reactions : Pause or slow the rate of injection, or permanently discontinue based on severity of the reaction. ( 5.2 ) Complications of Allogeneic HSCT: Fatal and other serious complications can occur in patients who receive allogeneic HSCT before or after being treated with a PD-1/PD-L1 blocking antibody. Follow patients closely for evidence of transplant-related complications and intervene promptly. ( 5.3 ) Embryo-Fetal Toxicity : Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and use of effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Severe and Fatal Immune-Mediated Adverse Reactions TECENTRIQ HYBREZA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death-receptor 1 (PD-1) or the 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. Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated 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 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 TECENTRIQ HYBREZA depending on severity [see Dosage and Administration (2.3) ]. In general, if TECENTRIQ HYBREZA 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 corticosteroid therapy. Toxicity management guidelines for adverse reactions that do not necessarily require systemic steroids (e.g., endocrinopathies and dermatologic reactions) are discussed below. Immune-Mediated Pneumonitis TECENTRIQ HYBREZA can cause immune-mediated pneumonitis, including fatal adverse reactions. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 2% (5/247) of patients with locally advanced or metastatic NSCLC receiving TECENTRIQ HYBREZA as monotherapy in the IMscin001 trial [see Adverse Reactions (6.1) ] , including Grade 2 (0.8%), and Grade 1 (1.2%) events. Pneumonitis led to the withholding of TECENTRIQ HYBREZA in one patient. Systemic corticosteroids were required in 40% (2/5) patients with pneumonitis who received TECENTRIQ HYBREZA as monotherapy. Pneumonitis resolved in both patients. The single patient in whom TECENTRIQ HYBREZA was withheld for pneumonitis reinitiated TECENTRIQ HYBREZA after symptom improvement. Intravenous Atezolizumab in Combination with Cobimetinib and Vemurafenib: Immune-mediated pneumonitis occurred in 13% (29/230) of patients receiving intravenous atezolizumab in combination with cobimetinib and vemurafenib in the IMspire150 trial [see Adverse Reactions (6.1) ], including Grade 3 (1.3%) and Grade 2 (7%) adverse reactions. Pneumonitis led to permanent discontinuation of intravenous atezolizumab in 2.6% of patients and withholding of intravenous atezolizumab in 7.4% of patients. Systemic corticosteroids were required in 55% (16/29) of patients with pneumonitis. Pneumonitis resolved in 97% of the 29 patients. Of the 17 patients in whom intravenous atezolizumab was withheld for pneumonitis, 10 reinitiated intravenous atezolizumab after symptom improvement; of these, 50% had recurrence of pneumonitis. Immune-Mediated Colitis TECENTRIQ HYBREZA can cause immune-mediated colitis, including Grade 3 adverse reactions. Colitis can present with diarrhea, abdominal pain, and lower gastrointestinal bleeding. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-Mediated Hepatitis TECENTRIQ HYBREZA can cause immune-mediated hepatitis, including fatal adverse reactions. Immune-mediated hepatitis occurred in 1.2% (3/247) of patients with locally advanced or metastatic NSCLC receiving TECENTRIQ HYBREZA as monotherapy in the IMscin001 trial [see Adverse Reactions (6.1) ] , including Grade 1 (0.4%) and Grade 3 (0.8%) events. Hepatitis led to the withholding of TECENTRIQ HYBREZA in 0.4% of patients. Systemic corticosteroids were required in 67% (2/3) of patients with hepatitis who received TECENTRIQ HYBREZA as monotherapy. Hepatitis resolved in 1 of the 3 patients. Intravenous Atezolizumab in Combination with Cobimetinib and Vemurafenib: Immune-mediated hepatitis occurred in 6.1% (14/230) of patients receiving intravenous atezolizumab in combination with cobimetinib and vemurafenib in the IMspire150 trial [see Adverse Reactions (6.1) ], including Grade 4 (1.3%), Grade 3 (1.7%) and Grade 2 (1.3%) adverse reactions. Hepatitis led to permanent discontinuation of intravenous atezolizumab in 2.2% and withholding of intravenous atezolizumab in 1.7% of patients. Systemic corticosteroids were required in 50% (7/14) of patients with hepatitis. Hepatitis resolved in 93% of the 14 patients. Of the 4 patients in whom intravenous atezolizumab was withheld for hepatitis, 3 reinitiated intravenous atezolizumab after symptom improvement; of these, 33% had recurrence of hepatitis. Immune-Mediated Endocrinopathies Adrenal Insufficiency: TECENTRIQ HYBREZA can cause primary or secondary adrenal insufficiency, including Grade 3 adverse reactions. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold or permanently discontinue TECENTRIQ HYBREZA depending on severity [see Dosage and Administration (2.3) ] . Immune-mediated adrenal insufficiency occurred in 0.8% (2/247) of patients with locally advanced or metastatic NSCLC receiving TECENTRIQ HYBREZA as monotherapy in the IMscin001 trial [see Adverse Reactions (6.1) ] , including Grade 2 (0.4%) adverse reactions. Adrenal insufficiency led to the withholding of TECENTRIQ HYBREZA in both patients. Systemic corticosteroids were required in 50% (1/2) of patients with adrenal…