14 ML atezolizumab 60 MG/ML Injection [Tecentriq]

INDICATIONS AND USAGE TECENTRIQ is a programmed death-ligand 1 (PD-L1) blocking antibody indicated: Non-Small Cell Lung Cancer (NSCLC) as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with Stage II to IIIA NSCLC whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-authorized test. ( 1.1 , 14.1 ) for the first-line treatment of adult patients with metastatic NSCLC whose tumors have high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 10% of the tumor area [IC ≥ 10%] ), as determined by an FDA-authorized test, with no EGFR or ALK genomic tumor aberrations. ( 1.1 ) in combination with bevacizumab, paclitaxel, and carboplatin, for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. ( 1.1 ) in combination with paclitaxel protein-bound and carboplatin for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations ( 1.1 ) for the treatment of adult patients with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving TECENTRIQ. ( 1.1 ) Small Cell Lung Cancer (SCLC) in combination with carboplatin and etoposide, for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). ( 1.2 ) in combination with lurbinectedin, for the maintenance treatment of adult patients with ES-SCLC whose disease has not progressed after first-line induction therapy with TECENTRIQ or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide. ( 1.2 ) Hepatocellular Carcinoma (HCC) in combination with bevacizumab for the treatment of adult patients with unresectable or metastatic HCC who have not received prior systemic therapy. ( 1.3 ) Melanoma in combination with cobimetinib and vemurafenib for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma. ( 1.4 ) Alveolar Soft Part Sarcoma (ASPS) for the treatment of adult and pediatric patients 2 years of age and older with unresectable or metastatic ASPS. ( 1.5 ) Muscle Invasive Bladder Cancer (MIBC) as adjuvant treatment of adult patients with MIBC after cystectomy who have circulating tumor DNA molecular residual disease (ctDNA MRD) as determined by an FDA-authorized test. ( 1.6 ) 1.1 Non-Small Cell Lung Cancer TECENTRIQ, as a single-agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage II to IIIA [see Clinical Studies (14.1) ] non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥ 1% of tumor cells, as determined by an FDA-authorized test [see Dosage and Administration (2.1) ]. TECENTRIQ, as a single agent, is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (PD-L1 stained ≥ 50% of tumor cells [TC ≥ 50%] or PD-L1 stained tumor-infiltrating immune cells [IC] covering ≥ 10% of the tumor area [IC ≥ 10%]), as determined by an FDA-authorized test, with no EGFR or ALK genomic tumor aberrations [see Dosage and Administration (2.1) ]. TECENTRIQ, in combination with bevacizumab, paclitaxel, and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. TECENTRIQ, in combination with paclitaxel protein-bound and carboplatin, is indicated for the first-line treatment of adult patients with metastatic non-squamous NSCLC with no EGFR or ALK genomic tumor aberrations. TECENTRIQ, as a single-agent, is indicated for the treatment of adult patients with metastatic NSCLC who have disease progression during or following platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for NSCLC harboring these aberrations prior to receiving TECENTRIQ. 1.2 Small Cell Lung Cancer TECENTRIQ, in combination with carboplatin and etoposide, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). TECENTRIQ, in combination with lurbinectedin, is indicated for the maintenance treatment of adult patients with ES-SCLC whose disease has not progressed after first-line induction therapy with TECENTRIQ or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide. 1.3 Hepatocellular Carcinoma TECENTRIQ, in combination with bevacizumab, is indicated for the treatment of adult patients with unresectable or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy. 1.4 Melanoma TECENTRIQ, in combination with cobimetinib and vemurafenib, is indicated for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma [see Dosage and Administration (2.1) ] . 1.5 Alveolar Soft Part Sarcoma TECENTRIQ, as a single agent, is indicated for the treatment of adult and pediatric patients 2 years of age and older with unresectable or metastatic alveolar soft part sarcoma (ASPS). 1.6 Muscle Invasive Bladder Cancer TECENTRIQ, as a single agent, is indicated as adjuvant treatment of adult patients with muscle invasive bladder cancer (MIBC) after cystectomy who have circulating tumor DNA molecular residual disease (ctDNA MRD) as determined by an FDA-authorized test [see Dosage and Administration (2.1) ] .

DOSAGE AND ADMINISTRATION Administer TECENTRIQ intravenously over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes. NSCLC In the adjuvant setting, administer TECENTRIQ following resection and up to 4 cycles of platinum-based chemotherapy as 840 mg every 2 weeks, 1200 mg every 3 weeks or 1680 mg every 4 weeks for up to 1 year. ( 2.2 ) In the metastatic setting, administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. ( 2.2 ) When administering with chemotherapy with or without bevacizumab, administer TECENTRIQ prior to chemotherapy and bevacizumab when given on the same day. ( 2.2 ) Small Cell Lung Cancer Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. Administer TECENTRIQ prior to chemotherapy when given on the same day. ( 2.2 ) Hepatocellular Carcinoma Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. Administer TECENTRIQ prior to bevacizumab when given on the same day. Bevacizumab is administered at 15 mg/kg every 3 weeks. ( 2.2 ) Melanoma Following completion of a 28-day cycle of cobimetinib and vemurafenib, administer TECENTRIQ 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks with cobimetinib 60 mg orally once daily (21 days on /7 days off) and vemurafenib 720 mg orally twice daily. ( 2.2 ) ASPS Adults: Administer TECENTRIQ as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks. ( 2.2 ) Pediatric patients 2 years of age and older: 15 mg/kg (up to a maximum of 1200 mg), every 3 weeks ( 2.2 ) MIBC Administer TECENTRIQ after cystectomy as 840 mg every 2 weeks, 1200 mg every 3 weeks, or 1680 mg every 4 weeks for up to 1 year. ( 2.2 ) 2.1 Patient Selection for Treatment of Non-Small Cell Lung Cancer, Melanoma, and Muscle Invasive Bladder Cancer Select patients with Stage II to IIIA non-small cell lung cancer for treatment with TECENTRIQ as a single agent based on PD-L1 expression on tumor cells [see Clinical Studies (14.1) ]. Select patients with first-line metastatic non-small cell lung cancer for treatment with TECENTRIQ as a single agent based on the PD-L1 expression on tumor cells or on tumor-infiltrating immune cells [see Clinical Studies (14.1) ]. Information on FDA-authorized tests for the determination of PD-L1 expression in metastatic non-small cell lung cancer are available at: http://www.fda.gov/CompanionDiagnostics. Select patients with unresectable or metastatic melanoma for treatment with TECENTRIQ in combination with cobimetinib and vemurafenib after confirming the presence of a BRAF V600 mutation [see Clinical Studies (14.4) ]. Information on FDA-authorized tests for the detection of BRAF V600 mutations in melanoma is available at: http://www.fda.gov/CompanionDiagnostics. Select patients with muscle invasive bladder cancer for treatment with TECENTRIQ as a single agent based on detection of ctDNA MRD in plasma via serial testing between six weeks and one year after cystectomy [see Clinical Studies (14.6) ]. Information on FDA-authorized tests for the determination of ctDNA MRD status in MIBC is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Recommended Dosage The recommended dosages of TECENTRIQ are presented in Table 1 . Administer TECENTRIQ as an intravenous infusion over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be delivered over 30 minutes. Table 1: Recommended Dosage of TECENTRIQ as a Single Agent Indication Recommended Dosage of TECENTRIQ Duration of Therapy Metastatic NSCLC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Until disease progression or unacceptable toxicity Adjuvant Treatment of NSCLC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Up to one year, unless there is disease recurrence or unacceptable toxicity ASPS (adult) 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Until disease progression or unacceptable toxicity ASPS (pediatric, 2 years of age and older) 15 mg/kg (up to a maximum 1200 mg) every 3 weeks MIBC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Up to one year, unless there is disease recurrence or unacceptable toxicity The recommended intravenous dosages of TECENTRIQ in combination with other therapeutic agents are presented in Table 2 . Refer to the respective Prescribing Information for each therapeutic agent administered in combination with TECENTRIQ for the recommended dosage information, as appropriate. Table 2: Recommended Dosage of TECENTRIQ in Combination with Other Therapeutic Agents Indication Recommended Dosage of TECENTRIQ Duration of Therapy NSCLC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Administer TECENTRIQ prior to chemotherapy and bevacizumab when given on the same day. Until disease progression or unacceptable toxicity SCLC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Administer TECENTRIQ prior to chemotherapy when given on the same day. HCC 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Administer TECENTRIQ prior to bevacizumab when given on the same day. Bevacizumab is administered at 15 mg/kg every 3 weeks. Melanoma 840 mg every 2 weeks or 1200 mg every 3 weeks or 1680 mg every 4 weeks Administer TECENTRIQ with cobimetinib 60 mg orally once daily (21 days on and 7 days off) and vemurafenib 720 mg orally twice daily. Prior to initiating TECENTRIQ, patients should receive a 28-day treatment cycle of cobimetinib 60 mg orally once daily (21 days on and 7 days off) and vemurafenib 960 mg orally twice daily from Days 1-21 and vemurafenib 720 mg orally twice daily from Days 22-28. 2.3 Dosage Modifications for Adverse Reactions No dose reduction for TECENTRIQ is recommended. In general, withhold TECENTRIQ for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue TECENTRIQ 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 or equivalent per day within 12 weeks of initiating steroids. Dosage modifications for TECENTRIQ for adverse reactions that require management different from these general guidelines are summarized in Table 3 . Table 3: Recommended Dosage Modifications for Adverse Reactions Adverse Reaction Severity Based on Common Terminology Criteria for Adverse Events (CTCAE), version 4 Dosage Modification ALT = alanine aminotransferase, AST = aspartate aminotransferase, ULN = upper limit normal, DRESS = Drug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens Johnson syndrome, TEN = toxic epidermal necrolysis Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] Pneumonitis Grade 2 Withhold Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to 10 mg per day or less (or equivalent) within 12 weeks of initiating steroids Grades 3 or 4 Permanently discontinue Colitis Grades 2 or 3 Withhold Grade 4 Permanently discontinue Hepatitis with no tumor involvement of the liver AST or ALT increases to more than 3 and up to 8 times ULN or Total bilirubin increases to more than 1.5 and up to 3 times ULN Withhold AST or ALT increases to more than 8 times ULN or Total bilirubin increases to more than 3 times ULN Permanently discontinue Hepatitis with tumor involvement of the liver If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue TECENTRIQ based on recommendations for hepatitis with no liver involvement Baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 t

WARNINGS AND PRECAUTIONS 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. ( 5.1 ) Withhold or permanently discontinue based on severity and type of reaction. ( 5.1 ). Infusion-Related Reactions : Interrupt, slow the rate of infusion, or permanently discontinue based on severity of infusion reactions. ( 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. ( 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 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 depending on severity [see Dosage and Administration (2.3) ]. In general, if TECENTRIQ 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 can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. TECENTRIQ as a Single Agent: Immune-mediated pneumonitis occurred in 3% (83/2616) of patients receiving TECENTRIQ as a single agent, including fatal (<0.1%), Grade 4 (0.2%), Grade 3 (0.8%), and Grade 2 (1.1%) adverse reactions. Pneumonitis led to permanent discontinuation of TECENTRIQ in 0.5% and withholding of TECENTRIQ in 1.5% of patients. Systemic corticosteroids were required in 55% (46/83) of patients with pneumonitis. Pneumonitis resolved in 69% of the 83 patients. Of the 39 patients in whom TECENTRIQ was withheld for pneumonitis, 25 reinitiated TECENTRIQ after symptom improvement; of these, 4% had recurrence of pneumonitis. In IMpower010 immune-mediated pneumonitis occurred in 3.8% (19/495) of patients receiving TECENTRIQ as a single agent, including fatal (0.2%), Grade 4 (0.2%), and Grade 3 (0.6%) adverse reactions. Pneumonitis led to permanent discontinuation of TECENTRIQ in 2.2% and withholding of TECENTRIQ in 0.8% of patients. Systemic corticosteroids were required in 63% (12/19) of patients with pneumonitis. Pneumonitis resolved in 84% of the 19 patients. TECENTRIQ in Combination with Cobimetinib and Vemurafenib: Immune-mediated pneumonitis occurred in 13% (29/230) of patients receiving TECENTRIQ in combination with cobimetinib and vemurafenib, including Grade 3 (1.3%) and Grade 2 (7%) adverse reactions. Pneumonitis led to permanent discontinuation of TECENTRIQ in 2.6% and withholding of TECENTRIQ 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 TECENTRIQ was withheld for pneumonitis, 10 reinitiated TECENTRIQ after symptom improvement; of these, 50% had recurrence of pneumonitis. Immune-Mediated Colitis TECENTRIQ can cause immune-mediated colitis. Colitis can present with diarrhea, abdominal pain, and lower gastrointestinal (GI) 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. TECENTRIQ as a Single Agent: Immune-mediated colitis occurred in 1% (26/2616) of patients receiving TECENTRIQ as a single agent, including Grade 3 (0.5%) and Grade 2 (0.3%) adverse reactions. Colitis led to permanent discontinuation of TECENTRIQ in 0.2% and withholding of TECENTRIQ in 0.5% of patients. Systemic corticosteroids were required in 50% (13/26) of patients with colitis. Colitis resolved in 73% of the 26 patients. Of the 12 patients in whom TECENTRIQ was withheld for colitis, 8 reinitiated treatment with TECENTRIQ after symptom improvement; of these, 25% had recurrence of colitis. Immune-Mediated Hepatitis TECENTRIQ can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.8% (48/2616) of patients receiving TECENTRIQ as a single agent, including fatal (<0.1%), Grade 4 (0.2%), Grade 3 (0.5%), and Grade 2 (0.5%) adverse reactions. Hepatitis led to permanent discontinuation of TECENTRIQ in 0.2% and withholding of TECENTRIQ in 0.2% of patients. Systemic corticosteroids were required in 25% (12/48) of patients with hepatitis. Hepatitis resolved in 50% of the 48 patients. Of the 6 patients in whom TECENTRIQ was withheld for hepatitis, 4 reinitiated treatment with TECENTRIQ after symptom improvement; of these, none had recurrence of hepatitis. TECENTRIQ in Combination with Cobimetinib and Vemurafenib: Immune-mediated hepatitis occurred in 6.1% (14/230) of patients receiving TECENTRIQ in combination with cobimetinib and vemurafenib, including Grade 4 (1.3%), Grade 3 (1.7%) and Grade 2 (1.3%) adverse reactions. Hepatitis led to permanent discontinuation of TECENTRIQ in 2.2% and withholding of TECENTRIQ 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 TECENTRIQ was withheld for hepatitis, 3 reinitiated TECENTRIQ after symptom improvement; of these, 33% had recurrence of hepatitis. Immune-Mediated Endocrinopathies Adrenal Insufficiency TECENTRIQ can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate sy

CONTRAINDICATIONS None. None. ( 4 )

Mechanism of Action PD L1 may be expressed on tumor cells and/or tumor infiltrating immune cells and can contribute to the inhibition of the anti-tumor immune response in the tumor microenvironment. Binding of PD L1 to the PD 1 and B7.1 receptors found on T cells and antigen presenting cells suppresses cytotoxic T-cell activity, T-cell proliferation and cytokine production. Atezolizumab is a monoclonal antibody that binds to PD L1 and blocks its interactions with both PD 1 and B7.1 receptors. This releases the PD L1/PD 1 mediated inhibition of the immune response, including activation of the anti-tumor immune response without inducing antibody-dependent cellular cytotoxicity. In syngeneic mouse tumor models, blocking PD L1 activity resulted in decreased tumor growth. In mouse models of cancer, dual inhibition of the PD-1/PD-L1 and MAPK pathways suppresses tumor growth and improves tumor immunogenicity through increased antigen presentation and T cell infiltration and activation compared to targeted therapy alone.