Tecentriq Hybreza

atezolizumab and hyaluronidase-tqjs · Injection · Subcutaneous

Prescription (Rx) Endoglycosidase Programmed Death Receptor-1 Blocking Antibody

Uses

1 INDICATIONS AND USAGE TECENTRIQ HYBREZA is a combination of atezolizumab, a programmed death-ligand 1 (PD-L1) blocking antibody, and hyaluronidase, an endoglycosidase 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 ) 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 HYBREZA. ( 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 HYBREZA or intravenous atezolizumab, and carboplatin plus 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 as determined by an FDA-approved test. ( 1.4 ) Alveolar Soft Part Sarcoma (ASPS) for the treatment of adult patients and pediatric patients (12 years of age and older who weigh 40 kg or greater) 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 HYBREZA, as monotherapy, 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 HYBREZA, as monotherapy, 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 HYBREZA, 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 HYBREZA, 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 HYBREZA, as monotherapy, 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 HYBREZA. 1.2 Small Cell Lung Cancer TECENTRIQ HYBREZA, 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 HYBREZA, 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 HYBREZA or intravenous atezolizumab, carboplatin and etoposide. 1.3 Hepatocellular Carcinoma TECENTRIQ HYBREZA, 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 HYBREZA, in combination with cobimetinib and vemurafenib, is indicated for the treatment of adult patients with BRAF V600 mutation-positive unresectable or metastatic melanoma as determined by an FDA-approved test [see Dosage and Administration (2.1) ] . 1.5 Alveolar Soft Part Sarcoma TECENTRIQ HYBREZA, as monotherapy, is indicated for the treatment of adult patients and pediatric patients (12 years of age and older who weigh 40 kg or greater) with unresectable or metastatic alveolar soft part sarcoma (ASPS).

Dosage and administration

2 DOSAGE AND ADMINISTRATION TECENTRIQ HYBREZA has different recommended dosage and administration than intravenous atezolizumab products. ( 2.2 ) TECENTRIQ HYBREZA is for subcutaneous use in the thigh only. ( 2.2 ) Do not administer TECENTRIQ HYBREZA intravenously. ( 2.2 ) The recommended dosage for adult patients and pediatric patients (12 years and older who weigh 40 kg or greater) is: TECENTRIQ HYBREZA 15 mL (1,875 mg atezolizumab and 30,000 units hyaluronidase) subcutaneously into the thigh over approximately 7 minutes every 3 weeks. ( 2.2 ) TECENTRIQ HYBREZA must be administered by a healthcare professional. ( 2.2 ) NSCLC Dosage In the adjuvant setting , administer TECENTRIQ HYBREZA following resection and up to 4 cycles of platinum-based chemotherapy every 3 weeks for up to 1 year. ( 2.3 ) In the metastatic setting , administer TECENTRIQ HYBREZA every 3 weeks. ( 2.3 ) When administering with chemotherapy with or without bevacizumab, administer TECENTRIQ HYBREZA prior to chemotherapy and bevacizumab when given on the same day. ( 2.3 ) SCLC Dosage Administer TECENTRIQ HYBREZA every 3 weeks. Administer TECENTRIQ HYBREZA prior to chemotherapy when given on the same day. ( 2.3 ) HCC Dosage Administer TECENTRIQ HYBREZA every 3 weeks. Administer TECENTRIQ HYBREZA prior to bevacizumab when given on the same day. Bevacizumab is administered intravenously at 15 mg/kg every 3 weeks. ( 2.3 ) Melanoma Dosage Following completion of a 28-day cycle of cobimetinib and vemurafenib, administer TECENTRIQ HYBREZA every 3 weeks with cobimetinib 60 mg orally once daily (21 days on /7 days off) and vemurafenib 720 mg orally twice daily. ( 2.3 ) ASPS Dosage Administer TECENTRIQ HYBREZA every 3 weeks. ( 2.3 ) MIBC Dosage Administer TECENTRIQ HYBREZA after cystectomy every 3 weeks for up to 1 year. ( 2.3 ) 2.1 Patient Selection for Treatment of Non-Small Cell Lung Cancer, Melanoma and Muscle Invasive Bladder Cancer Select adult patients with: Stage II to IIIA NSCLC for adjuvant treatment with TECENTRIQ HYBREZA as a monotherapy (following tumor resection and platinum-based chemotherapy) based on PD-L1 expression on tumor cells [see Clinical Studies (14.1) ]. Metastatic NSCLC for first-line treatment with TECENTRIQ HYBREZA as monotherapy based on the PD-L1 expression on tumor cells or on tumor-infiltrating immune cells [see Clinical Studies (14.1) ]. Unresectable or metastatic melanoma for treatment with TECENTRIQ HYBREZA in combination with cobimetinib and vemurafenib after confirming the presence of a BRAF V600 mutation [see Clinical Studies (14.4) ]. MIBC for treatment with TECENTRIQ HYBREZA, as a monotherapy 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 PD-L1 expression in metastatic NSCLC, for detection of BRAF V600 mutations in melanoma, or for the determination of ctDNA MRD status in MIBC is available at: http://www.fda.gov/CompanionDiagnostics. 2.2 Important Dosage and Administration Information TECENTRIQ HYBREZA has different recommended dosage and administration than intravenous atezolizumab products. To reduce the risk of medication errors, prior to administration, check the vial labels to ensure that the drug being prepared is subcutaneously administered TECENTRIQ HYBREZA and not intravenously administered atezolizumab. Do not substitute TECENTRIQ HYBREZA for or with intravenous atezolizumab products because they have different recommended dosages. Adult patients who are treated with intravenous atezolizumab can switch to subcutaneous TECENTRIQ HYBREZA at their next scheduled dose. Adult patients who are treated with TECENTRIQ HYBREZA can switch to intravenous atezolizumab at their next scheduled dose. Pediatric patients 12 years of age and older who weigh 40 kg or greater and are treated with intravenous atezolizumab can switch to subcutaneous TECENTRIQ HYBREZA at their next scheduled dose [see Indications and Usage (1.5) ]. Pediatric patients who are treated with TECENTRIQ HYBREZA can switch to intravenous atezolizumab at their next scheduled dose. TECENTRIQ HYBREZA is for subcutaneous use in the thigh only. Administer over approximately 7 minutes. Inject in healthy skin and never into areas where the skin is red, bruised, tender, or hard. When possible, alternate injections between the left and right thigh. Ensure the injection site is at least 2.5 cm from the previous site. Do not administer TECENTRIQ HYBREZA intravenously. TECENTRIQ HYBREZA must be administered by a healthcare professional. Do not administer the remaining volume in the tubing to the patient. If using concomitant subcutaneous drugs, administer at sites other than the thighs. 2.3 Recommended Dosage and Administration Instructions The recommended dosage of TECENTRIQ HYBREZA in adult patients and pediatric patients (12 years of age and older who weigh 40 kg or greater) is one 15 mL injection (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase, referred to as TECENTRIQ HYBREZA) administered subcutaneously in the thigh over approximately 7 minutes every 3 weeks. The recommended dosage for pediatric patients 12 years of age and older who weigh less than 40 kg has not been established [see Use in Specific Populations (8.4) , Clinical Pharmacology (12.3) ]. Administration instructions for TECENTRIQ HYBREZA as monotherapy and in combination with other therapeutic agents are presented in Table 1 . For the recommended dosage of each therapeutic agent administered in combination with TECENTRIQ HYBREZA refer to the product's respective Prescribing Information.

Dosage forms and strengths

Injection: 1,875 mg atezolizumab and 30,000 units hyaluronidase per 15 mL (125 mg and 2,000 units per mL) clear to slightly opalescent, and colorless to slightly yellow solution in a single-dose vial. Injection : 1,875 mg atezolizumab and 30,000 units hyaluronidase per 15 mL (125 mg/2,000 units per mL) solution in a single-dose vial. ( 3 )

Contraindications

4 CONTRAINDICATIONS TECENTRIQ HYBREZA is contraindicated in patients with known hypersensitivity to hyaluronidase or to any of its excipients. TECENTRIQ HYBREZA is contraindicated in patients with known hypersensitivity to hyaluronidase or any of its excipients. ( 4 )

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. 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.

Side effects

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) ] Most common adverse reactions (AR) (≥ 10%) with TECENTRIQ HYBREZA as monotherapy in patients with NSCLC were fatigue, musculoskeletal pain, cough, dyspnea, and decreased appetite. ( 6.1 ) Safety of TECENTRIQ HYBREZA for the approved NSCLC, EC-SCLC, HCC, melanoma, ASPS, and MIBC indications is based on safety of intravenous atezolizumab in these populations. Most common AR with intravenous atezolizumab are presented below by indication and regimen ( 6.1 ): Most common AR (≥ 20%) as monotherapy were: First-line NSCLC : fatigue/asthenia. Metastatic NSCLC : fatigue/asthenia, cough, decreased appetite, dyspnea, and myalgia/pain. ASPS : musculoskeletal pain, fatigue, rash, cough, headache, nausea, hypertension, vomiting, constipation, dyspnea, dizziness, hemorrhage, diarrhea, insomnia, abdominal pain hypothyroidism, pyrexia, anxiety, arrhythmia and decreased appetite. MIBC: urinary tract infection. Most common AR (≥ 20%) in combination with other antineoplastic drugs were: NSCLC (with bevacizumab, paclitaxel, and carboplatin): neuropathy fatigue/asthenia, alopecia, myalgia, nausea, diarrhea, constipation, decreased appetite, arthralgia, hypertension, rash, cough. Non-squamous NSCLC (with paclitaxel protein-bound and carboplatin): fatigue/asthenia, nausea, diarrhea, myalgia/pain, constipation, neuropathy, alopecia, dyspnea, decreased appetite, cough, vomiting and rash. SCLC (with chemotherapy): fatigue/asthenia, nausea, alopecia, decreased appetite, constipation and vomiting. HCC (with bevacizumab): hypertension, fatigue and proteinuria. Melanoma (with cobimetinib and vemurafenib): rash, musculoskeletal pain, fatigue, hepatotoxicity, pyrexia, nausea, pruritus, edema, stomatitis, hypothyroidism, and photosensitivity reaction. 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. Adverse Reactions of TECENTRIQ HYBREZA in Adult Patients with NSCLC The safety of TECENTRIQ HYBREZA was evaluated in IMscin001, open-label, multi-center, international, randomized trial for patients with locally advanced or metastatic NSCLC who have not been exposed to cancer immunotherapy and who have had disease progression on prior platinum-based therapy [see Clinical Studies (14.1) ] . Patients with previously treated metastatic non-small cell lung cancer (NSCLC) either received TECENTRIQ HYBREZA (containing 1,875 mg of atezolizumab and 30,000 units of hyaluronidase) administered subcutaneously into the thigh over approximately 7 minutes every 3 weeks or intravenous atezolizumab every 3 weeks until disease progression or unacceptable toxicity. Among 247 patients who received TECENTRIQ HYBREZA, 32% were exposed for 6 months or longer and 8% were exposed for greater than one year. The median age was 64 years (range: 27 to 85); 69% male; 67% White, 22% Asian, 0.8% Black or African American; 74% were non-Hispanic or Latino; 26% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 74% had an ECOG PS of 1; and 70% of patients were current or previous smokers. Serious adverse reactions occurred in 19% of patients who received TECENTRIQ HYBREZA. Serious adverse reactions (> 1%) included pneumonia, myocardial infarction, and pleural effusion. Fatal adverse reactions occurred in 6% of patients who received TECENTRIQ HYBREZA, including pneumonia (2.4%), myocardial infarction (1.2%), head injury (0.4%), ischemic stroke (0.4%), pleural effusion (0.4%), pulmonary embolism (0.4%), respiratory tract infection (0.4%), sepsis (0.4%), and toxic epidermal necrolysis (0.4%). Permanent discontinuation of TECENTRIQ HYBREZA due to an adverse reaction occurred in 3.6% of patients. Adverse reactions which resulted in permanent discontinuation of TECENTRIQ HYBREZA in > 1% of patients included pneumonia (2%). Dosage interruptions of TECENTRIQ HYBREZA due to an adverse reaction occurred in 32% of patients. Adverse reactions which required dosage interruption in > 1% of patients were COVID-19 (4.9%), increased aspartate aminotransferase (2.8%), increased alanine aminotransferase (2.4%), pneumonia (2.4%), anemia (1.6%), dyspnea (1.6%), fatigue (1.2%), and viral respiratory tract infection (1.2%). The most common adverse reactions of any grade (occurring in ≥ 10% of patients) were fatigue (19%), musculoskeletal pain (15%), cough (13%), dyspnea (12%), and decreased appetite (11%). Tables 3 and 4 summarize adverse reactions and selected laboratory abnormalities, respectively in TECENTRIQ HYBREZA-treated patients in IMscin001.

Use in specific populations

Lactation : Advise not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1) ] , TECENTRIQ HYBREZA can cause fetal harm when administered to a pregnant woman . There are no available data on the use of TECENTRIQ HYBREZA in pregnant women. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus resulting in fetal death (see Data ) . Advise females of reproductive potential of the potential risk to a fetus [see Warnings and Precautions (5.4) ] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data: TECENTRIQ HYBREZA for subcutaneous injection contains atezolizumab and hyaluronidase [see Description (11) ] . Atezolizumab : Animal reproduction studies have not been conducted with atezolizumab to evaluate its effect on reproduction and fetal development. A literature-based assessment of the effects on reproduction demonstrated that a central function of the PD-L1/PD-1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to a fetus. Blockage of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to a fetus and to result in an increase in fetal loss; therefore, potential risks of administering atezolizumab during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-L1/PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to atezolizumab may increase the risk of developing immune-mediated disorders or altering the normal immune response. Hyaluronidase : In an embryo-fetal study, mice were dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase (recombinant human) at dose levels up to 2,200,000 U/kg, which is > 2,400 times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is > 400 times higher than the human dose. In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous injection, with hyaluronidase (recombinant human) from implantation through lactation and weaning at dose levels up to 1,100,000 U/kg, which is > 1,200 times higher than the human dose. The study found no adverse effects on sexual maturation, learning and memory or fertility of the offspring. 8.2 Lactation Risk Summary There is no information regarding the presence of atezolizumab or hyaluronidase in human milk or its effects on the breastfed child, or on milk production. Maternal IgG is known to be present in human milk. The effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to TECENTRIQ HYBREZA are unknown. Because of the potential for serious adverse reactions in breastfed children from TECENTRIQ HYBREZA, advise women not to breastfeed during treatment with TECENTRIQ HYBREZA and for 5 months after the last dose. 8.3 Females and Males of Reproductive Potential Based on its mechanism of action, TECENTRIQ HYBREZA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Pregnancy Testing Verify pregnancy status in females of reproductive potential prior to initiating TECENTRIQ HYBREZA [see Warnings and Precautions (5.4) and Use in Specific Populations (8.1) ] . Contraception Females: Advise females of reproductive potential to use effective contraception during treatment with TECENTRIQ HYBREZA and for 5 months following the last dose. Infertility Females: Based on animal studies, TECENTRIQ HYBREZA may impair fertility in females of reproductive potential while receiving TECENTRIQ HYBREZA treatment [see Nonclinical Toxicology (13.1) ] . 8.4 Pediatric Use Alveolar Soft Part Sarcoma The safety and effectiveness of TECENTRIQ HYBREZA as monotherapy for the treatment of pediatric patients (12 years of age and older who weigh 40 kg or greater) with unresectable or metastatic alveolar soft part sarcoma (ASPS) has been established. Use of TECENTRIQ HYBREZA for this pediatric indication is supported by evidence from adequate and well controlled studies of intravenous atezolizumab in adults, and additional pharmacokinetic and safety data for intravenous atezolizumab in pediatric patients 12 years and older [see Adverse Reactions (6.1) and Clinical Studies (14) ] . Atezolizumab exposures following subcutaneous administration of TECENTRIQ HYBREZA (containing 1,875 mg of atezolizumab) every 3 weeks in pediatric patients 12 years of age and older who weigh 40 kg or greater are predicted to be within the range of those observed in adults at the same dosage. The safety and effectiveness of TECENTRIQ HYBREZA have not been established in pediatric patients <12 years of age with unresectable or metastatic ASPS. Solid Tumors and Lymphomas The safety and effectiveness of TECENTRIQ HYBREZA in pediatric patients have not been established for other approved indications. 8.5 Geriatric Use TECENTRIQ HYBREZA as a Single-Agent Of 247 adult patients treated with TECENTRIQ HYBREZA as monotherapy in IMscin001, 45% were 65 years and over and 10% were 75 years and over. No overall differences in safety or effectiveness of TECENTRIQ HYBREZA have been observed between patients aged 65 years or older and younger adult patients.

Pregnancy

8.1 Pregnancy Risk Summary Based on its mechanism of action [see Clinical Pharmacology (12.1) ] , TECENTRIQ HYBREZA can cause fetal harm when administered to a pregnant woman . There are no available data on the use of TECENTRIQ HYBREZA in pregnant women. Animal studies have demonstrated that inhibition of the PD-L1/PD-1 pathway can lead to increased risk of immune-related rejection of the developing fetus resulting in fetal death (see Data ) . Advise females of reproductive potential of the potential risk to a fetus [see Warnings and Precautions (5.4) ] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data: TECENTRIQ HYBREZA for subcutaneous injection contains atezolizumab and hyaluronidase [see Description (11) ] . Atezolizumab : Animal reproduction studies have not been conducted with atezolizumab to evaluate its effect on reproduction and fetal development. A literature-based assessment of the effects on reproduction demonstrated that a central function of the PD-L1/PD-1 pathway is to preserve pregnancy by maintaining maternal immune tolerance to a fetus. Blockage of PD-L1 signaling has been shown in murine models of pregnancy to disrupt tolerance to a fetus and to result in an increase in fetal loss; therefore, potential risks of administering atezolizumab during pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there were no malformations related to the blockade of PD-L1/PD-1 signaling in the offspring of these animals; however, immune-mediated disorders occurred in PD-1 and PD-L1 knockout mice. Based on its mechanism of action, fetal exposure to atezolizumab may increase the risk of developing immune-mediated disorders or altering the normal immune response. Hyaluronidase : In an embryo-fetal study, mice were dosed daily by subcutaneous injection during the period of organogenesis with hyaluronidase (recombinant human) at dose levels up to 2,200,000 U/kg, which is > 2,400 times higher than the human dose. The study found no evidence of teratogenicity. Reduced fetal weight and increased numbers of fetal resorptions were observed, with no effects found at a daily dose of 360,000 U/kg, which is > 400 times higher than the human dose. In a peri-and post-natal reproduction study, mice have been dosed daily by subcutaneous injection, with hyaluronidase (recombinant human) from implantation through lactation and weaning at dose levels up to 1,100,000 U/kg, which is > 1,200 times higher than the human dose. The study found no adverse effects on sexual maturation, learning and memory or fertility of the offspring.

Pediatric use

8.4 Pediatric Use Alveolar Soft Part Sarcoma The safety and effectiveness of TECENTRIQ HYBREZA as monotherapy for the treatment of pediatric patients (12 years of age and older who weigh 40 kg or greater) with unresectable or metastatic alveolar soft part sarcoma (ASPS) has been established. Use of TECENTRIQ HYBREZA for this pediatric indication is supported by evidence from adequate and well controlled studies of intravenous atezolizumab in adults, and additional pharmacokinetic and safety data for intravenous atezolizumab in pediatric patients 12 years and older [see Adverse Reactions (6.1) and Clinical Studies (14) ] . Atezolizumab exposures following subcutaneous administration of TECENTRIQ HYBREZA (containing 1,875 mg of atezolizumab) every 3 weeks in pediatric patients 12 years of age and older who weigh 40 kg or greater are predicted to be within the range of those observed in adults at the same dosage. The safety and effectiveness of TECENTRIQ HYBREZA have not been established in pediatric patients <12 years of age with unresectable or metastatic ASPS. Solid Tumors and Lymphomas The safety and effectiveness of TECENTRIQ HYBREZA in pediatric patients have not been established for other approved indications.

Geriatric use

8.5 Geriatric Use TECENTRIQ HYBREZA as a Single-Agent Of 247 adult patients treated with TECENTRIQ HYBREZA as monotherapy in IMscin001, 45% were 65 years and over and 10% were 75 years and over. No overall differences in safety or effectiveness of TECENTRIQ HYBREZA have been observed between patients aged 65 years or older and younger adult patients. The safety of TECENTRIQ HYBREZA as monotherapy or in combination with other antineoplastic drugs for its approved indications [see Indications and Usage (1.1 , 1.2 , 1.3 , 1.4 , 1.5 , 1.6) ] has been established in adequate and well-controlled studies of intravenous atezolizumab as a single agent and in combination with other antineoplastic drugs. Below is a description of geriatric use information from the intravenous atezolizumab studies. Intravenous Atezolizumab as a Single-Agent Of 2,616 adult patients with metastatic NSCLC and other tumor types treated with monotherapy intravenous atezolizumab in clinical studies, 49% were 65 years and over and 15% were 75 years and over. Of the 167 patients with MIBC treated with intravenous atezolizumab in IMvigor011, 117 (70%) patients were 65 years of age and older and 44 (26%) patients were 75 years of age and older. No overall differences in safety or effectiveness were observed between intravenous atezolizumab-treated patients aged 65 years or older and younger patients. Intravenous Atezolizumab in Combination with Other Antineoplastic Drugs Of 2,421 adult patients with NSCLC and EC-SCLC treated with intravenous atezolizumab in combination with other antineoplastic drugs in clinical studies, 48% were 65 years and over and 10% were 75 years and over. No overall differences in safety or effectiveness were observed between intravenous atezolizumab-treated patients aged 65 years or older and younger adult patients. Intravenous Atezolizumab in Combination with Lurbinectedin Of 242 adult patients with ES-SCLC treated with intravenous atezolizumab in combination with lurbinectedin in IMforte, 124 (51%) patients were 65 years of age and older, while 29 (12%) patients were 75 years of age and older. No overall differences in effectiveness were observed between older and younger patients. There was a higher incidence of Grade 3 or 4 adverse reactions (45% vs 31%) and treatment discontinuation (11% vs 0.8%) in patients ≥ 65 years of age compared to younger patients, respectively.

Description

11 DESCRIPTION TECENTRIQ HYBREZA is a fixed-combination drug product containing atezolizumab and hyaluronidase (human recombinant). Atezolizumab is a programmed cell death ligand 1 (PD-L1) blocking antibody. Atezolizumab is an Fc-engineered, humanized, non-glycosylated IgG1 kappa immunoglobulin that has a calculated molecular mass of 145 kDa. Hyaluronidase (human recombinant) is an endoglycosidase used to increase the dispersion and absorption of co-administered drugs administered subcutaneously. It is a glycosylated single-chain protein produced by mammalian (Chinese Hamster Ovary) cells containing a DNA plasmid encoding for a soluble fragment of human hyaluronidase (PH20). Hyaluronidase (human recombinant) has a molecular weight of approximately 61 kDa. TECENTRIQ HYBREZA (atezolizumab and hyaluronidase-tqjs) injection for subcutaneous use is a sterile, preservative-free, clear and slightly opalescent, and colorless to slightly yellow solution in single-dose vials. Each 15 mL single-dose vial contains 1,875 mg of atezolizumab, 30,000 units of hyaluronidase, histidine (46.5 mg), methionine (22.4 mg), polysorbate 20 (9 mg), sucrose (1,232 mg), and water for injection, adjusted to pH 5.8 with acetic acid.

Mechanism of action

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. Hyaluronan is a polysaccharide found in the extracellular matrix of the subcutaneous tissue. It is depolymerized by the naturally occurring enzyme hyaluronidase. Unlike the stable structural components of the interstitial matrix, hyaluronan has a half-life of approximately 0.5 days. Hyaluronidase increases permeability of the subcutaneous tissue by depolymerizing hyaluronan. In the doses administered, hyaluronidase in TECENTRIQ HYBREZA acts transiently and locally. The effects of hyaluronidase are reversible and permeability of the subcutaneous tissue is restored within 24 to 48 hours.

How supplied

(atezolizumab and hyaluronidase-tqjs) injection for subcutaneous use is a sterile, preservative-free, clear to slightly opalescent, and colorless to slightly yellow solution. It is supplied in a carton containing: 1,875 mg and 30,000 units/15 mL (125 mg and 2,000 units/mL) in a single-dose vial (NDC 50242-933-01). Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.

Storage

Store vials under refrigeration at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze. Do not shake.

Patient information

Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Immune-Mediated Adverse Reactions Inform patients of the risk of immune-mediated adverse reactions that may require corticosteroid treatment and interruption or discontinuation of TECENTRIQ HYBREZA, including: Pneumonitis: Advise patients to contact their healthcare provider immediately for any new or worsening cough, chest pain, or shortness of breath [see Warnings and Precautions (5.1) ] . Colitis: Advise patients to contact their healthcare provider immediately for diarrhea, blood or mucus in stools, or severe abdominal pain [see Warnings and Precautions (5.1) ] . Hepatitis: Advise patients to contact their healthcare provider immediately for jaundice, severe nausea or vomiting, pain on the right side of abdomen, lethargy, or easy bruising or bleeding [see Warnings and Precautions (5.1) ] . Endocrinopathies: Advise patients to contact their healthcare provider immediately for signs or symptoms of hypophysitis, hyperthyroidism, hypothyroidism, adrenal insufficiency, or type 1 diabetes mellitus, including diabetic ketoacidosis [see Warnings and Precautions (5.1) ] . Nephritis: Advise patients to contact their healthcare provider immediately for pelvic pain, frequent urination, or unusual swelling [see Warnings and Precautions (5.1) ] . Dermatologic Adverse Reactions: Advise patients to contact their healthcare provider immediately for generalized rash, skin eruption, or painful skin and mucous membrane lesions [see Warnings and Precautions (5.1) ] . Other Immune-Mediated Adverse Reactions: Advise patients to contact their healthcare provider immediately for signs or symptoms of other potential immune-mediated adverse reactions [see Warnings and Precautions (5.1) ]. Advise patients of the risk of solid organ transplant rejection and other transplant (including corneal graft) rejection. Advise patients to contact their healthcare provider immediately for signs and symptoms of organ transplant rejection and other transplant (including corneal graft) rejection [see Warnings and Precautions (5.1) ]. Infusion-Related Reactions Advise patients to contact their healthcare provider immediately for signs or symptoms of infusion-related reactions [see Warnings and Precautions (5.2) ] . Complications of Allogeneic HSCT after PD-1/PD-L1 Inhibitors 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 [see Warnings and Precautions (5.3) ] . Embryo-Fetal Toxicity Advise females of reproductive potential that TECENTRIQ HYBREZA can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1 , 8.3) ] . Advise females of reproductive potential to use effective contraception during treatment and for 5 months after the last dose of TECENTRIQ HYBREZA [see Use in Specific Populations (8.3) ] . Lactation Advise female patients not to breastfeed while taking TECENTRIQ HYBREZA and for 5 months after the last dose [see Use in Specific Populations (8.2) ] .

Label text from the FDA structured product label by Genentech, Inc. (revised May 20, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Tecentriq Hybreza NDC products (1)

NDCStrength & formLabelerType
50242-933Atezolizumab 1875 mg/15mL; Hyaluronidase (human Recombinant) 30000 U/15mL
Injection		Genentech, Inc.BLA

Frequently asked questions

What is Tecentriq Hybreza used for?

1 INDICATIONS AND USAGE TECENTRIQ HYBREZA is a combination of atezolizumab, a programmed death-ligand 1 (PD-L1) blocking antibody, and hyaluronidase, an endoglycosidase 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…

What are the side effects of Tecentriq Hybreza?

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) ] Most common adverse reactions (AR) (≥ 10%) with… See the full label for the complete list.

Who makes Tecentriq Hybreza?

Tecentriq Hybreza is listed by 1 labeler in the FDA NDC directory, including Genentech, Inc..