Atezolizumab

1 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

12.1 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.

2 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 e

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Severe and Fatal Immune-Mediated Adverse Reactions [see Warnings and Precautions (5.1) ] Infusion-Related Reactions [see Warnings and Precautions (5.2) ] Complications of Allogeneic HSCT after PD-1/PD-L1 Inhibitors [see Warnings and Precautions (5.3) ] TECENTRIQ as a single-agent Most common adverse reactions (≥ 20%) with TECENTRIQ as a single-agent are fatigue/asthenia, decreased appetite, nausea, cough, and dyspnea. ( 6.1 ) TECENTRIQ in combination with other antineoplastic drugs Most common adverse reactions (≥ 20%) in patients with NSCLC and SCLC are fatigue/asthenia, nausea, alopecia, constipation, diarrhea, and decreased appetite. ( 6.1 ) TECENTRIQ in combination with bevacizumab Most common adverse reactions (≥ 20%) in patients with HCC are hypertension, fatigue and proteinuria. ( 6.1 ) TECENTRIQ in combination with cobimetinib and vemurafenib Most common adverse reactions (≥ 20%) with TECENTRIQ in patients with melanoma are rash, musculoskeletal pain, fatigue, hepatotoxicity, pyrexia, nausea, pruritus, edema, stomatitis, hypothyroidism, and photosensitivity reaction. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 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 data described in WARNINGS AND PRECAUTIONS reflect exposure to TECENTRIQ as a single-agent in 2616 patients in two randomized, active-controlled studies (POPLAR, OAK) and three open-label, single arm studies (PCD4989g, BIRCH, FIR) which enrolled 1636 patients with metastatic NSCLC, and 980 patients with other tumor types. TECENTRIQ was administered at a dose of 1200 mg intravenously every 3 weeks in all studies except PCD4989g. Among the 2616 patients who received a single-agent TECENTRIQ, 36% were exposed for longer than 6 months and 20% were exposed for longer than 12 months. Using the dataset described for patients who received TECENTRIQ as a single-agent, the most common adverse reactions in ≥ 20% of patients were fatigue/asthenia (48%), decreased appetite (25%), nausea (24%), cough (22%), and dyspnea (22%). In addition, the data reflect exposure to TECENTRIQ as a single agent as adjuvant therapy in 495 patients with early-stage NSCLC enrolled in a randomized study (IMpower010). In addition, the data reflect exposure to TECENTRIQ in combination with other antineoplastic drugs in 2421 patients with NSCLC (N = 2223) or SCLC (N = 198) enrolled in five randomized, active-controlled trials, including IMpower150, IMpower130 and IMpower133. Among the 2421 patients, 53% were exposed to TECENTRIQ for longer than 6 months and 29% were exposed to TECENTRIQ for longer than 12 months. Among the 2421 patients with NSCLC and SCLC who received TECENTRIQ in combination with other antineoplastic drugs, the most common adverse reactions in ≥20% of patients were fatigue/asthenia (49%), nausea (38%), alopecia (35%), constipation (29%), diarrhea (28%) and decreased appetite (27%). The data also reflect exposure to TECENTRIQ administered in combination with cobimetinib and vemurafenib in 230 patients enrolled in IMspire150. Among the 230 patients, 62% were exposed to TECENTRIQ for longer than 6 months and 42% were exposed to TECENTRIQ for longer than 12 months. Non-Small Cell Lung Cancer (NSCLC) Adjuvant Treatment of Early-stage NSCLC IMpower010 The safety of TECENTRIQ was evaluated in IMpower010, a multicenter, open-label, randomized trial for the adjuvant treatment of patients with stage IB (tumors ≥ 4 cm) - IIIA NSCLC who had complete tumor resection and received up to 4 cycles of cisplatin-based adjuvant chemotherapy. Patients recei

5 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.

4 CONTRAINDICATIONS None. None. ( 4 )