Genentech is excited to share the news of the Food and Drug Administration (FDA) approval of TECENTRIQ® (atezolizumab) as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage II-IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥1% of tumor cells, as determined by an FDA-approved test.

INDICATION

TECENTRIQ, as a single agent, is indicated as adjuvant treatment following resection and platinum-based chemotherapy for adult patients with stage II-IIIA non-small cell lung cancer (NSCLC) whose tumors have PD-L1 expression on ≥1% of tumor cells, as determined by an FDA-approved test.

IMPORTANT SAFETY INFORMATION

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 can occur in any organ system or tissue and at any time after starting TECENTRIQ. While immune-mediated adverse reactions usually manifest during treatment with TECENTRIQ, they can also manifest after discontinuation of treatment.

Early identification and management of immune-mediated adverse reactions are

essential to ensure safe use of TECENTRIQ. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions.

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, then 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.

Immune-Mediated Pneumonitis

● TECENTRIQ can cause immune-mediated pneumonitis. The incidence of

pneumonitis is higher in patients who have received prior thoracic radiation

● Immune-mediated pneumonitis occurred in 3.8% (19/495) of patients with

NSCLC receiving TECENTRIQ alone as adjuvant treatment, including fatal

(0.2%), Grade 4 (0.2%), and Grade 3 (0.6%) adverse reactions

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

● Immune-mediated colitis occurred in 1% (26/2616) of patients receiving

TECENTRIQ alone, including Grade 3 (0.5%) and Grade 2 (0.3%) adverse

reactions

Immune-Mediated Hepatitis

● TECENTRIQ can cause immune-mediated hepatitis

● Immune-mediated hepatitis occurred in 1.8% (48/2616) of patients receiving

TECENTRIQ alone, including fatal (<0.1%), Grade 4 (0.2%), Grade 3

(0.5%), and Grade 2 (0.5%) adverse reactions

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

● TECENTRIQ can cause primary or secondary adrenal insufficiency. For

Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment,

including hormone replacement as clinically indicated

● Adrenal insufficiency occurred in 1.2% (6/495) of patients with NSCLC

receiving TECENTRIQ alone as adjuvant treatment, including Grade 3

(0.4%) adverse reactions

● Hypophysitis

● TECENTRIQ can cause immune-mediated hypophysitis. Hypophysitis can

present with acute symptoms associated with mass effect such as

headache, photophobia, or visual field cuts. Hypophysitis can cause

hypopituitarism. Initiate hormone replacement as clinically indicated

● Hypophysitis occurred in <0.1% (2/2616) of patients receiving TECENTRIQ

alone, including Grade 2 (1 patient, <0.1%) adverse reactions

Thyroid Disorders

● TECENTRIQ can cause immune-mediated thyroid disorders. Thyroiditis can

present with or without endocrinopathy. Hypothyroidism can follow

hyperthyroidism. Initiate hormone replacement for hypothyroidism or

medical management for hyperthyroidism as clinically indicated

Thyroiditis occurred in 1.2% (6/495) of patients with NSCLC receiving

TECENTRIQ alone as adjuvant treatment, including Grade 2 (0.4%)

adverse reactions. Thyroiditis led to withholding of TECENTRIQ in 1 patient

● Hyperthyroidism occurred in 6% (32/495) of patients with NSCLC receiving

TECENTRIQ alone as adjuvant treatment, including Grade 3 (0.4%)

adverse reactions

● Hypothyroidism occurred in 17% (86/495) of patients with NSCLC receiving

TECENTRIQ alone as adjuvant treatment

Type 1 Diabetes Mellitus, Which Can Present With Diabetic Ketoacidosis

● Initiate treatment with insulin as clinically indicated

● Type 1 diabetes mellitus occurred in 0.3% (7/2616) of patients receiving

TECENTRIQ alone, including Grade 3 (0.2%) and Grade 2 (<0.1%) adverse

reactions

Immune-Mediated Nephritis With Renal Dysfunction

● TECENTRIQ can cause immune-mediated nephritis

● Immune-mediated nephritis with renal dysfunction occurred in <0.1% (1/2616)

of patients receiving TECENTRIQ alone, and this adverse reaction was a

Grade 3 (<0.1%) adverse reaction

Immune-Mediated Dermatologic Adverse Reactions

● TECENTRIQ can cause immune-mediated rash or dermatitis. Exfoliative

dermatitis, including Stevens-Johnson syndrome (SJS), DRESS, and toxic

epidermal necrolysis (TEN), has occurred with PD-1/PD-L1 blocking antibodies.

Topical emollients and/or topical corticosteroids may be adequate to treat mild

to moderate non-exfoliative rashes

● Immune-mediated dermatologic adverse reactions occurred in 0.6% (15/2616)

of patients receiving TECENTRIQ alone, including Grade 3 (<0.1%) and Grade

2 (0.2%) adverse reactions

Other Immune-Mediated Adverse Reactions

● The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% (unless otherwise noted) in patients who received TECENTRIQ or were reported with the use of other PD-1/PD-L1 blocking antibodies

○ Cardiac/Vascular: Myocarditis, pericarditis, vasculitis

○ Nervous System: Meningitis, encephalitis, myelitis and demyelination,

myasthenic syndrome/myasthenia gravis (including exacerbation),

Guillain-Barr. 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 to include increases in serum amylase and

lipase levels, gastritis, duodenitis

○ Musculoskeletal and Connective Tissue: Myositis/polymyositis,

rhabdomyolysis and associated sequelae including renal failure,

arthritis, polymyalgia rheumatic

○ Endocrine: Hypoparathyroidism

○ 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

Infusion-Related Reactions

● TECENTRIQ can cause severe or life-threatening infusion-related reactions.

Interrupt, slow the rate of infusion, or permanently discontinue based on

severity

● Infusion-related reactions occurred in 1.3% of patients, including Grade 3

(0.2%) reactions

Complications of Allogeneic HSCT After PD-1/PD-L1 Inhibitors

● 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. Consider the benefits versus risks of treatment with a PD-

1/PD-L1 blocking antibody prior to or after an allogeneic HSCT

Embryo-Fetal Toxicity

● TECENTRIQ can cause fetal harm when administered to a pregnant woman

● Verify pregnancy status of females of reproductive potential prior to initiating

TECENTRIQ

● Advise females of reproductive potential of the potential risk to a fetus and to

use effective contraception during treatment with TECENTRIQ and for at least 5

months after the last dose

Most Common Adverse Reactions

The most common adverse reactions (rate ≥20%) in patients who received

TECENTRIQ alone were fatigue/asthenia (48%), decreased appetite (25%), nausea (24%), cough (22%), and dyspnea (22%).

Use in Specific Populations

Advise female patients not to breastfeed during treatment and for at least 5 months after the last dose.

You may report side effects to the FDA at 1-800-FDA-1088 or

www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety

Information.