Tecentriq

Name: Tecentriq

Side Effects of Tecentriq

Serious side effects have been reported with Tecentriq. See the “Drug Precautions” section.

Common side effects of Tecentriq include the following:

  • feeling tired
  • decreased appetite
  • nausea
  • urinary tract infection
  • fever
  • constipation

This is not a complete list of side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tecentriq Interactions

No drug interactions have been determined by the manufacturer. However, you should tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Not all drug interactions are known or reported and new drug interactions are continually being reported.

Tecentriq Interactions

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Other drugs may interact with atezolizumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

What other drugs will affect atezolizumab?

Other drugs may interact with atezolizumab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Tecentriq Dosage and Administration

General

Restricted Distribution

  • Obtain atezolizumab through a limited network of specialty distributors.3 5

  • Contact manufacturer at 800-551-22313 or consult the Tecentriq website () for specific availability information.5

Administration

IV Administration

For solution compatibility information, see Compatibility under Stability.

Administer by IV infusion.1 Do not administer by rapid IV injection (e.g., IV push or bolus).1

Atezolizumab injection concentrate must be diluted prior to administration.1 Immediate administration recommended.1 (See Storage under Stability.)

Do not infuse simultaneously through the same IV line with other drugs.1

Use of low-protein-binding 0.2- to 0.22-mcm inline filter is optional.1

Dilution

Undiluted solution should be colorless to slightly yellow.1 Do not use if it is cloudy or discolored or if particulate matter is present.1

Do not shake vial.1

Withdraw 20 mL of atezolizumab injection concentrate (containing 60 mg/mL) and dilute in a PVC, polyethylene, or polyolefin infusion bag containing 250 mL of 0.9% sodium chloride.1 Do not use any other diluent.1 Mix the diluted solution by gentle inversion; do not shake.1 Discard any partially used vial.1

Rate of Administration

Initial dose: Administer over 60 minutes.1

Subsequent doses: Administer over 30 minutes (if first infusion well tolerated).1

Dosage

Adults

Urothelial Carcinoma IV

1.2 g every 3 weeks.1 Continue therapy until disease progression or unacceptable toxicity occurs.1

NSCLC IV

1.2 g every 3 weeks.1 Continue therapy until disease progression or unacceptable toxicity occurs.1

Therapy Interruption for Toxicity Immune-mediated Pneumonitis IV

If grade 2 immune-mediated pneumonitis occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Pneumonitis under Cautions.)

If grade 3 or 4 immune-mediated pneumonitis occurs, discontinue drug.1

Immune-mediated Hepatic Effects IV

For grade 2 immune-mediated hepatitis, serum ALT or AST elevations >3 times but ≤5 times the ULN, or total bilirubin concentrations >1.5 times but ≤3 times the ULN, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Hepatic Effects under Cautions.)

For grade 3 or 4 immune-mediated hepatitis, ALT or AST elevations >5 times the ULN, or total bilirubin concentrations >3 times the ULN, discontinue drug.1

Immune-mediated GI Effects IV

If grade 2 or 3 immune-mediated colitis or diarrhea occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated GI Effects under Cautions.)

If grade 4 immune-mediated colitis or diarrhea occurs, discontinue drug.1

Immune-mediated Endocrine Effects IV

If symptomatic immune-mediated hypophysitis, adrenal insufficiency, hypothyroidism, or hyperthyroidism occurs or if grade 3 or 4 immune-mediated hyperglycemia occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Immune-mediated Endocrine Effects under Cautions.)

If grade 4 immune-mediated hypophysitis occurs, discontinue drug.1

Other Immune-mediated Adverse Effects IV

If grade 2 immune-mediated ocular inflammatory toxicity, grade 2 or 3 immune-mediated pancreatitis, or grade 3 or 4 elevations in amylase or lipase concentrations (>2 times the ULN) occur, interrupt therapy until toxicity resolves to grade 0 or 1.1 (See Other Immune-mediated Effects under Cautions.)

If myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, meningoencephalitis, grade 3 or 4 immune-mediated ocular inflammatory toxicity, grade 4 immune-mediated pancreatitis, or recurrent immune-mediated pancreatitis of any severity occurs, discontinue drug.1

Infusion-related Reactions IV

If grade 2 infusion-related reactions occur, interrupt infusion until reaction resolves to grade 0 or 1.1 (See Infusion-related Effects under Cautions.)

If grade 3 or 4 infusion-related reactions occur, discontinue drug.1

Infectious Complications IV

If grade 3 or 4 infection occurs, interrupt therapy.1 (See Infectious Complications under Cautions.)

Dermatologic Effects IV

If grade 3 rash occurs, interrupt therapy until toxicity resolves to grade 0 or 1.1

If grade 4 rash occurs, discontinue drug.1

Special Populations

Hepatic Impairment

Mild hepatic impairment: No dosage adjustment required.1 (See Special Populations under Pharmacokinetics.)

Moderate or severe hepatic impairment: No dosage recommendations at this time.1

Renal Impairment

Mild, moderate, or severe renal impairment: No dosage adjustment required.1 (See Special Populations under Pharmacokinetics.)

Geriatric Patients

No special dosage recommendations at this time.1 (See Geriatric Use under Cautions.)

Actions

  • An IgG1 kappa immunoglobulin that is selective for PD-L1.1 2 4

  • Overexpression of PD-1 ligands on surface of tumor cells results in activation of PD-1 and B7.1 and suppression of cytotoxic T-cell activity, T-cell proliferation, and cytokine production.1 8 9 10

  • Blocks interaction between PD-L1 and the receptors PD-1 and B7.1, resulting in activation of antitumor immune response without inducing antibody-dependent cell-mediated cytotoxicity (ADCC).1 10

Before Using Tecentriq

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of atezolizumab injection in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of atezolizumab injection in the elderly.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

  • Diabetes or
  • Immune system problems (eg, Crohn's disease, ulcerative colitis, lupus) or
  • Infection or
  • Liver problems or
  • Lung or breathing problems or
  • Nervous system problems (eg, Guillain-Barré syndrome, myasthenia gravis) or
  • Pancreatitis (inflammation of the pancreas) or
  • Thyroid problems—Use with caution. May make these conditions worse.

Precautions While Using Tecentriq

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.

Using this medicine while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant during treatment and for at least 5 months after the last dose of this medicine. If you think you have become pregnant while using the medicine, tell your doctor right away.

Tell your doctor right away if you have a cough, chest tightness, or any type of breathing problem with this medicine. These could be symptoms of a serious lung problem.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, a loss of appetite, nausea, unusual tiredness or weakness, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Colitis (inflammation of the colon) may occur with this medicine. Tell your doctor right away if you have stomach pain or tenderness, watery or bloody diarrhea, or a fever after using the medicine.

Adrenal, pituitary, or thyroid gland problems may occur while you are using this medicine. Tell your doctor if you have changes in mood or behavior, constipation, dry skin or hair, feeling cold, sensitivity to heat, sweating, trouble sleeping, or weight changes.

Check with your doctor if you have a headache, confusion, seizures, stiff neck, vomiting while you are using this medicine. These may be symptoms of encephalitis.

Check with your doctor right away if you have severe headache, drowsiness, confusion, general feeling of illness, or stiff neck or back while you are using this medicine. These may be symptoms of meningitis.

Call your doctor right away if you have difficulty with breathing, swallowing, or talking, muscle weakness, severe tiredness, or sudden numbness and weakness in the arms or legs. These could be symptoms of a nervous system problem.

Tell your doctor right away if you have a blurred vision, eye pain or redness, or other vision problems while you are using this medicine.

Pancreatitis may occur while you are using this medicine. Tell your doctor right away if you have sudden and severe stomach pain, chills, constipation, nausea, vomiting, fever, or lightheadedness.

Call your doctor right away if you start to have a cough that won't go away, weight loss, night sweats, fever, chills, painful or difficult urination, or flu-like symptoms, such as a runny or stuffy nose, headache, blurred vision, or feeling generally ill. These may be signs that you have an infection.

This medicine may cause a rare but serious type of an allergic reaction called an infusion reaction. This can be life-threatening and requires immediate medical attention. Tell your doctor right away if you start to have a skin rash, dizziness, trouble breathing, chest tightness, swelling in your face or hands, fever or chills while you are receiving this medicine.

Talk with your doctor before receiving this medicine if you plan to have children. Some women who use this medicine have become infertile (unable to have children).

Indications and Usage for Tecentriq

Locally Advanced or Metastatic Urothelial Carcinoma

Tecentriq (atezolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who:

  • are not eligible for cisplatin-containing chemotherapy, or
  • have disease progression during or following any platinum-containing chemotherapy, or within 12 months of neoadjuvant or adjuvant chemotherapy

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials [see Clinical Studies (14.1)].

Metastatic Non-Small Cell Lung Cancer

Tecentriq is indicated for the treatment of patients with metastatic non-small cell lung cancer (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 these aberrations prior to receiving Tecentriq [see Clinical Studies (14.2)].

Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections of the label:

  • Immune-Related Pneumonitis [see Warnings and Precautions (5.1)]
  • Immune-Related Hepatitis [see Warnings and Precautions (5.2)]
  • Immune-Related Colitis [see Warnings and Precautions (5.3)]
  • Immune-Related Endocrinopathies [see Warnings and Precautions (5.4)]
  • Other Immune-Related Adverse Reactions [see Warnings and Precautions (5.5)]
  • Infection [see Warnings and Precautions (5.6)]
  • Infusion-Related Reactions [see Warnings and Precautions (5.7)]

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.

Urothelial Carcinoma

Cisplatin-Ineligible Patients with Locally Advanced or Metastatic Urothelial Carcinoma

The safety of Tecentriq was evaluated in Study 4, a multicenter, open-label, single-arm trial that included 119 patients with locally advanced or metastatic urothelial carcinoma who were ineligible for cisplatin-containing chemotherapy and were either previously untreated or had disease progression at least 12 months after neoadjuvant or adjuvant chemotherapy [see Clinical Studies (14.1)]. Patients received 1200 mg of Tecentriq intravenously every 3 weeks until either unacceptable toxicity or disease progression. The median duration of exposure was 15.0 weeks (range 0, 87 weeks).

The most common adverse reactions (≥ 20%) were fatigue (52%), decreased appetite (24%), diarrhea (24%), and nausea (22%). The most common Grade 3–4 adverse reactions (≥ 2%) were fatigue, urinary tract infection, anemia, diarrhea, blood creatinine increase, intestinal obstruction, ALT increase, hyponatremia, decreased appetite, sepsis, back/neck pain, renal failure, and hypotension.

Five patients (4.2%) who were treated with Tecentriq experienced one of the following events which led to death: sepsis, cardiac arrest, myocardial infarction, respiratory failure, or respiratory distress. One additional patient (0.8%) was experiencing herpetic meningoencephalitis and disease progression at the time of death. Tecentriq was discontinued for adverse reactions in 4.2% (5/119) of patients. The adverse reactions leading to discontinuation were diarrhea/colitis (1.7%), fatigue (0.8%), hypersensitivity (0.8%), and dyspnea (0.8%). Adverse reactions leading to interruption of Tecentriq occurred in 35% of patients, the most common (≥ 1%) were intestinal obstruction, fatigue, diarrhea, urinary tract infection, infusion related reaction, cough, abdominal pain, peripheral edema, pyrexia, respiratory tract infection, upper respiratory tract infection, creatinine increase, decreased appetite, hyponatremia, back pain, pruritus, and venous thromboembolism. Serious adverse reactions occurred in 37% of patients. The most frequent serious adverse reactions (≥ 2%) were diarrhea, intestinal obstruction, sepsis, acute kidney injury, and renal failure.

Immune-related adverse reactions requiring systemic corticosteroids or hormone replacement therapy occurred in 19.3% (23/119) patients, including 12.6% (15/119) patients who required systemic corticosteroid therapy and 6.7% (8/119) patients who required only hormone replacement therapy.

Six patients (5.0%) received an oral prednisone dose equivalent to ≥40 mg daily for an immune-mediated adverse reaction [see Warnings and Precautions (5)].

Table 1 summarizes the adverse reactions that occurred in ≥ 10% of patients and Table 2 summarizes Grade 3–4 selected laboratory abnormalities that occurred in ≥ 1% of patients treated with Tecentriq in Study 4.

Table 1: All Grade Adverse Reactions in ≥ 10% of Patients with Urothelial Carcinoma in Study 4
Tecentriq
N = 119
Adverse Reaction All Grades
(%)
Grades 3–4
(%)
* Includes fatigue, asthenia, lethargy, and malaise † Includes edema peripheral, scrotal edema, lymphedema, and edema ‡ Includes diarrhea, colitis, frequent bowel movements, autoimmune colitis § Includes abdominal pain, upper abdominal pain, lower abdominal pain, and flank pain ¶ Includes decreased appetite and early satiety # Includes rash, dermatitis, dermatitis acneiform, rash maculo-papular, rash erythematous, rash pruritic, rash macular, and rash papular Þ Includes urinary tract infection, urinary tract infection bacterial, cystitis, and urosepsis ß Includes cough and productive cough à Includes dyspnea and exertional dyspnea
General Disorders
Fatigue* 52 8
Peripheral edema† 17 2
Pyrexia 14 0.8
Gastrointestinal Disorders
Diarrhea‡ 24 5
Nausea 22 2
Vomiting 16 0.8
Constipation 15 2
Abdominal pain§ 15 0.8
Metabolism and Nutrition Disorders
Decreased appetite¶ 24 3
Musculoskeletal and Connective Tissue Disorders
Back/Neck pain 18 3
Arthralgia 13 0
Skin and Subcutaneous Tissue Disorders
Pruritus 18 0.8
Rash# 17 0.8
Infections
Urinary tract infectionÞ 17 5
Respiratory, Thoracic, and Mediastinal Disorders
Coughß 14 0
Dyspneaà 12 0
Table 2: Grade 3–4 Laboratory Abnormalities in Patients with Urothelial Carcinoma in Study 4 in ≥ 1% of Patients
Laboratory Test Grades 3–4
(%)
Hyponatremia 15
Hyperglycemia 10
Lymphopenia 9
Anemia 7
Increased Alkaline phosphatase 7
Increased Creatinine 5
Hypophosphatemia 4
Increased ALT 4
Increased AST 4
Hyperkalemia 3
Hypermagnesemia 3
Hyperbilirubinemia 3

Previously Treated Patients with Locally Advanced or Metastatic Urothelial Carcinoma

The safety of Tecentriq was evaluated in Study 1, a multicenter, open-label, single-arm trial that included 310 patients in a single arm trial with locally advanced or metastatic urothelial carcinoma who had disease progression during or following at least one platinum-containing chemotherapy regimen or who had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen [see Clinical Studies (14.1)]. Patients received 1200 mg of Tecentriq intravenously every 3 weeks until unacceptable toxicity or either radiographic or clinical progression. The median duration of exposure was 12.3 weeks (range: 0.1, 46 weeks).

The most common adverse reactions (≥ 20%) were fatigue (52%), decreased appetite (26%), nausea (25%), urinary tract infection (22%), pyrexia (21%), and constipation (21%). The most common Grade 3–4 adverse reactions (≥ 2%) were urinary tract infection, anemia, fatigue, dehydration, intestinal obstruction, urinary obstruction, hematuria, dyspnea, acute kidney injury, abdominal pain, venous thromboembolism, sepsis, and pneumonia.

Three patients (1.0%) who were treated with Tecentriq experienced one of the following events which led to death: sepsis, pneumonitis, or intestinal obstruction. Tecentriq was discontinued for adverse reactions in 3.2% (10/310) of the 310 patients. Sepsis led to discontinuation in 0.6% (2/310) of patients. Adverse reactions leading to interruption of Tecentriq occurred in 27% of patients; the most common (> 1%) were liver enzyme increase, urinary tract infection, diarrhea, fatigue, confusional state, urinary obstruction, pyrexia, dyspnea, venous thromboembolism, and pneumonitis. Serious adverse reactions occurred in 45% of patients. The most frequent serious adverse reactions (> 2%) were urinary tract infection, hematuria, acute kidney injury, intestinal obstruction, pyrexia, venous thromboembolism, urinary obstruction, pneumonia, dyspnea, abdominal pain, sepsis, and confusional state.

Immune-related adverse reactions requiring systemic corticosteroids or hormone replacement therapy occurred in 11.0% (34/310) patients, including 8.4% (26/310) patients who required systemic corticosteroid therapy and 2.6% (8/310) patients who required only hormone replacement therapy.

Eighteen patients (5.8%) received an oral prednisone dose equivalent to ≥40 mg daily for an immune-mediated adverse reaction [see Warnings and Precautions (5)].

Table 3 summarizes the adverse reactions that occurred in ≥ 10% of patients while Table 4 summarizes Grade 3–4 selected laboratory abnormalities that occurred in ≥ 1% of patients treated with Tecentriq in Study 1.

Table 3: All Grade Adverse Reactions in ≥ 10% of Patients with Urothelial Carcinoma in Study 1
Tecentriq
N=310
Adverse Reaction All Grades
(%)
Grades 3–4
(%)
Gastrointestinal Disorders
Nausea 25 2
Constipation 21 0.3
Diarrhea 18 1
Abdominal pain 17 4
Vomiting 17 1
General Disorders
Fatigue 52 6
Pyrexia 21 1
Peripheral edema 18 1
Infections
Urinary tract infection 22 9
Metabolism and Nutrition Disorders
Decreased appetite 26 1
Musculoskeletal and Connective Tissue Disorders
Back/Neck pain 15 2
Arthralgia 14 1
Renal and urinary disorders
Hematuria 14 3
Respiratory, Thoracic, and Mediastinal Disorders
Dyspnea 16 4
Cough 14 0.3
Skin and Subcutaneous Tissue Disorders
Rash 15 0.3
Pruritus 13 0.3
Table 4: Grade 3–4 Laboratory Abnormalities in Patients with Urothelial Carcinoma in Study 1 in ≥ 1% of Patients
Laboratory Test Grades 3–4
(%)
Lymphopenia 10
Hyponatremia 10
Anemia 8
Hyperglycemia 5
Increased Alkaline phosphatase 4
Increased Creatinine 3
Increased ALT 2
Increased AST 2
Hypoalbuminemia 1

NSCLC

The safety of Tecentriq was evaluated in Study 3, a multicenter, international, randomized, open-label trial in patients with metastatic NSCLC who progressed during or following a platinum-containing regimen, regardless of PD-L1 expression [see Clinical Studies (14.2)]. Patients received 1200 mg of Tecentriq (n=142) administered intravenously every 3 weeks until unacceptable toxicity or either radiographic or clinical progression or docetaxel (n=135) administered intravenously at 75 mg/m2 every 3 weeks until unacceptable toxicity or disease progression. The median duration of exposure was 3.7 months (range: 0–19 months) in Tecentriq-treated patients and 2.1 months (range: 0–17 months) in docetaxel-treated patients.

The most common adverse reactions (≥ 20%) in patients receiving Tecentriq were fatigue (46%), decreased appetite (35%), dyspnea (32%), cough (30%), nausea (22%), musculoskeletal pain (22%), and constipation (20%). The most common Grade 3-4 adverse reactions (≥2%) were dyspnea, pneumonia, hypoxia, hyponatremia, fatigue, anemia, musculoskeletal pain, AST increase, ALT increase, dysphagia, and arthralgia.

Nine patients (6.3%) who were treated with Tecentriq experienced either pulmonary embolism (2), pneumonia (2), pneumothorax, ulcer hemorrhage, cachexia secondary to dysphagia, myocardial infarction, or large intestinal perforation which led to death. Tecentriq was discontinued due to adverse reactions in 4% (6/142) of patients. Adverse reactions leading to interruption of Tecentriq occurred in 24% of patients; the most common (>1%) were pneumonia, liver function test abnormality, upper respiratory tract infection, pneumonitis, acute kidney injury, hypoxia, hypothyroidism, dyspnea, anemia, and fatigue. Serious adverse reactions occurred in 37% of patients. The most frequent serious adverse reactions (> 2%) were pneumonia, dyspnea, pleural effusion, pyrexia, and venous thromboembolism.

Table 5 summarizes adverse reactions that occurred in at least 10% of Tecentriq-treated patients and at a higher incidence than in the docetaxel arm. Table 6 summarizes selected laboratory abnormalities worsening from baseline that occurred in ≥10% of Tecentriq-treated patients and at a higher incidence than in the docetaxel arm.

Table 5: Adverse Reactions Occurring in ≥10% of Tecentriq-Treated Patients with NSCLC and at a Higher Incidence than in the Docetaxel Arm (Between Arm Difference of ≥5% [All Grades] or ≥2% [Grades 3–4]) (Study 3)
Tecentriq
(n=142)
Docetaxel
(n=135)
Adverse Reaction All grades Grade 3–4 All grades Grade 3–4
Percentage (%) of Patients
General Disorders
Pyrexia 18 0 13 0
Infections
Pneumonia 18 6 4 2
Metabolism and nutrition disorders
Decreased appetite 35 1 22 0
Musculoskeletal and connective tissue disorders
Arthralgia 16 2 9 2
Back pain 14 1 9 1
Psychiatric Disorders
Insomnia 14 0 8 2
Respiratory, thoracic and mediastinal disorders
Dyspnea 32 7 24 2
Cough 30 1 25 0
Table 6: Selected Laboratory Abnormalities Worsening from Baseline Occurring in ≥10% of Tecentriq-Treated Patients with NSCLC and at a Higher Incidence than in the Docetaxel Arm (Between Arm Difference of ≥5% [All Grades] or ≥2% [Grades 3–4]) (Study 3)
Percentage of Patients with Worsening
Laboratory Test from Baseline
Tecentriq Docetaxel
Test All grades
%
Grade 3–4
%
All grades
%
Grade 3–4
%
Hyponatremia 48 13 28 8
Hypoalbuminemia 48 5 49 1
Alkaline Phosphatase increased 42 2 24 1
Aspartate aminotransferase increased 33 2 15 0
Alanine aminotransferase increased 31 2 9 1
Creatinine increased 19 1 14 2
Hypokalemia 18 2 11 4
Hypercalcemia 13 0 5 0
Total Bilirubin increased 11 0 5 1

Immunogenicity

As with all therapeutic proteins, there is a potential for immunogenicity. Among 275 patients in Study 1, 114 patients (41.5%) tested positive for treatment-emergent (treatment-induced or treatment-enhanced) anti-therapeutic antibodies (ATA) at one or more post-dose time points. Among 135 patients in Study 3, 73 patients (54.1%) tested positive for treatment-emergent ATAs at one or more post-dose time points. Among 111 patients in Study 4, 53 patients (47.7%) tested positive for treatment-emergent ATAs at one or more post-dose time points. In Study 1, Study 3, and Study 4, the presence of ATAs did not appear to have a clinically significant impact on pharmacokinetics, safety or efficacy.

Immunogenicity assay results are highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of incidence of ATAs to Tecentriq with the incidence of antibodies to other products may be misleading.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

No studies have been performed to test the potential of atezolizumab for carcinogenicity or genotoxicity.

Animal fertility studies have not been conducted with atezolizumab; however, an assessment of the male and female reproductive organs was included in a 26-week, repeat-dose toxicity study in cynomolgus monkeys. Weekly administration of atezolizumab to female monkeys at the highest dose tested caused an irregular menstrual cycle pattern and a lack of newly formed corpora lutea in the ovaries. This effect occurred at an estimated AUC approximately 6 times the AUC in patients receiving the recommended dose and was reversible. There was no effect on the male monkey reproductive organs.

Animal Toxicology and/or Pharmacology

In animal models, inhibition of PD-L1/PD-1 signaling increased the severity of some infections and enhanced inflammatory responses. M. tuberculosis-infected PD-1 knockout mice exhibit markedly decreased survival compared with wild-type controls, which correlated with increased bacterial proliferation and inflammatory responses in these animals. PD-L1 and PD-1 knockout mice and mice receiving PD-L1 blocking antibody have also shown decreased survival following infection with lymphocytic choriomeningitis virus.

What is Tecentriq?

Tecentriq (atezolizumab) is a monoclonal antibody that affects the actions of the body's immune system. Atezolizumab strengthens your immune system to help your body fight against tumor cells.

Tecentriq is used to treat a certain type of bladder cancer that has spread to other parts of the body or cannot be removed by surgery.

Tecentriq is also used to treat non-small cell lung cancer that has spread to other parts of the body.

Tecentriq is usually given after other cancer medicines have been tried without success.

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