Tecentriq

Antineoplastic Monoclonal Antibodies Targeting Programmed Death-1 (PD-1) and Programmed Death-Ligand 1 (PD-L1) Pathways

Emetic Risk
Minimal

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Dilution
Withdraw the required volume of atezolizumab from the vial(s).
Dilute to a final concentration between 3.2 mg/mL and 16.8 mg/mL in a polyvinyl chloride (PVC), polyethylene (PE), or polyolefin (PO) infusion bag containing 0.9% Sodium Chloride Injection.
Mix by gentle inversion; do not shake.
Storage after dilution: Store diluted solution at room temperature for no more than 6 hours (including infusion time), or under refrigeration (2 to 8 degrees C; 36 to 46 degrees F) for no more than 24 hours from the time of preparation.[60793]
 
Infusion
Administer atezolizumab prior to chemotherapy or other antineoplastic agents when given on the same day.
Do not infuse through the same IV line with other drugs.
Administer the first dose intravenously, with or without a sterile, non-pyrogenic, low protein-binding in-line filter (0.2 to 0.22 micron), over 60 minutes; do not administer atezolizumab as an IV push or bolus. If tolerated, all subsequent infusions may be infused over 30 minutes.
Interrupt or slow administration for grade 2 infusion-related reactions; the infusion may resume when symptoms have resolved to grade 0 or 1.
Permanently discontinue atezolizumab for grade 3 or 4 infusion-related reactions.[60793]

rash / Early / 0-27.0
hypermagnesemia / Delayed / 0-26.0
hypophosphatemia / Delayed / 0-22.0
hyperamylasemia / Delayed / 0-20.0
hyponatremia / Delayed / 0-15.0
hypertension / Early / 0-15.0
hypercalcemia / Delayed / 0-14.0
hyperglycemia / Delayed / 0-10.0
lymphopenia / Delayed / 0-9.0
hyperbilirubinemia / Delayed / 0-8.0
weight gain / Delayed / 0-6.0
fatigue / Early / 0-5.0
dyspnea / Early / 0-4.9
nausea / Early / 0-4.0
headache / Early / 0-4.0
dizziness / Early / 0-4.0
asthenia / Delayed / 0-4.0
hyperkalemia / Delayed / 0-3.9
hypomagnesemia / Delayed / 0-3.4
anemia / Delayed / 0-3.0
hypocalcemia / Delayed / 0-3.0
pulmonary embolism / Delayed / 0-3.0
vomiting / Early / 0-2.7
infusion-related reactions / Rapid / 0.2-2.4
anorexia / Delayed / 0-2.0
fever / Early / 0-2.0
bleeding / Early / 0-2.0
constipation / Delayed / 0-1.1
cough / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
hemolytic anemia / Delayed / 0-1.0
myelitis / Delayed / 0-1.0
uveitis / Delayed / 0-1.0
pruritus / Rapid / 0-1.0
edema / Delayed / 0-1.0
pericarditis / Delayed / 0-1.0
vasculitis / Delayed / 0-1.0
myocarditis / Delayed / 0-1.0
organ transplant rejection / Delayed / 0-1.0
hyperthyroidism / Delayed / 0-0.4
hypothyroidism / Delayed / 0-0.3
diabetes mellitus / Delayed / 0.2-0.2
interstitial nephritis / Delayed / 0-0.1
pleural effusion / Delayed / 1.0
GI obstruction / Delayed / Incidence not known
bowel ischemia / Delayed / Incidence not known
visual impairment / Early / Incidence not known
retinal detachment / Delayed / Incidence not known
Vogt-Koyanagi-Harada syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
pericardial effusion / Delayed / Incidence not known
cardiac tamponade / Delayed / Incidence not known
hypertensive crisis / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
ventricular tachycardia / Early / Incidence not known
bradycardia / Rapid / Incidence not known
stroke / Early / Incidence not known
intracranial bleeding / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
veno-occlusive disease (VOD) / Delayed / Incidence not known
sinusoidal obstruction syndrome (SOS) / Delayed / Incidence not known
graft-versus-host disease (GVHD) / Delayed / Incidence not known
ocular hemorrhage / Delayed / Incidence not known

antibody formation / Delayed / 13.0-36.0
hypoglycemia / Early / 0-33.0
thrombocytosis / Delayed / 0-29.0
hepatotoxicity / Delayed / 0-29.0
iritis / Delayed / 0-1.0
sarcoidosis / Delayed / 0-1.0
gastritis / Delayed / 0-1.0
hypoparathyroidism / Delayed / 0-1.0
peripheral neuropathy / Delayed / 0-0.4
confusion / Early / 2.0
glossitis / Early / Incidence not known
oral ulceration / Delayed / Incidence not known
dehydration / Delayed / Incidence not known
psoriaform rash / Delayed / Incidence not known
palmar-plantar erythrodysesthesia (hand and foot syndrome) / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known
proteinuria / Delayed / Incidence not known
hyperphosphatemia / Delayed / Incidence not known
hypernatremia / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
QT prolongation / Rapid / Incidence not known
hemoptysis / Delayed / Incidence not known
hematuria / Delayed / Incidence not known

insomnia / Early / 0-27.0
anxiety / Delayed / 0-25.0
influenza / Delayed / 0-18.0
weight loss / Delayed / 0-18.0
rhinitis / Early / 0-16.0
purpura / Delayed / 0-1.0
cheilitis / Delayed / Incidence not known
dysesthesia / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
acneiform rash / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
lichen planus-like eruption / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
syncope / Early / Incidence not known
vertigo / Early / Incidence not known
epistaxis / Delayed / Incidence not known
dysgeusia / Early / Incidence not known

Tecentriq

Rx

Programmed death ligand-1 (PD-L1) blocking monoclonal antibody
Used in adults for certain types of melanoma, hepatocellular cancer, and lung cancer; also used in adult and pediatric patients aged 2 years and older for alveolar soft part sarcoma
Immune-mediated reactions have been reported; treatment may need to be withheld or permanently discontinued

840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity. Administer in combination with bevacizumab (15 mg/kg IV), paclitaxel (200 mg/m2 IV, or 175 mg/m2 IV in Asian patients), and carboplatin (AUC 6 IV), every 3 weeks for a maximum of 4 to 6 cycles of chemotherapy. Administer atezolizumab prior to bevacizumab and chemotherapy when given on the same day. In a multicenter, randomized, open-label, phase 3 clinical trial (IMpower150), treatment with atezolizumab plus bevacizumab/paclitaxel/carboplatin (ABCP) significantly improved overall survival in patients with metastatic nonsquamous NSCLC compared with BCP without atezolizumab (19.2 months vs. 14.7 months); overall survival with atezolizumab/paclitaxel/carboplatin was not significantly different from BCP. Progression-free survival was also significantly improved in the ABCP arm compared with BCP (8.5 months vs. 7 months). The objective response rate was 55% (complete response [CR], 4%) versus 42% (CR, 1%), respectively, for a median duration of 10.8 months and 6.5 months, respectively.[60793] [63819]

840 mg IV every 2 weeks until disease progression or unacceptable toxicity; alternatively, atezolizumab may be dosed at 1,200 mg IV every 3 weeks OR atezolizumab 1,680 mg IV every 4 weeks. In clinical trials, atezolizumab could be continued beyond disease progression, as long as clinical benefit was evident. In a multicenter, randomized, open-label phase 2 clinical trial, second-line treatment of platinum-resistant NSCLC with atezolizumab significantly improved overall survival compared with docetaxel (12.6 months vs. 9.7 months); progression-free survival (PFS) and objective response rate (ORR) were not significantly different. In a pre-planned subgroup analysis, the benefit of atezolizumab was greater in patients with 1% or more PD-L1 expressing tumor cells or tumor-infiltrating cells. Atezolizumab was better tolerated than docetaxel.[61208]

840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity. Administer in combination with nab-paclitaxel (100 mg/m2 on days 1, 8, and 15) and carboplatin (AUC 6 IV on day 1), every 3 weeks for a maximum of 4 to 6 cycles of chemotherapy. Administer atezolizumab prior to chemotherapy when given on the same day. First-line treatment of EGFR- and ALK-negative metastatic NSCLC with atezolizumab plus nab-paclitaxel and carboplatin significantly improved median overall survival (18.6 months vs. 13.9 months) and median progression-free survival (7.2 months vs. 6.5 months) compared with nab-paclitaxel and carboplatin alone in a multicenter, randomized, open-label trial (IMpower130). The overall response rate was 46% (complete response [CR], 5%) in the atezolizumab arm compared with 32% (CR, 1%) in the control arm, for a median duration of 10.8 months versus 7.8 months, respectively.

840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity. Treatment with atezolizumab significantly improved median overall survival compared with platinum-based chemotherapy (20.2 months vs. 13.1 months) in patients with metastatic NSCLC and high PD-L1 expression, without EGFR or ALK mutations in a randomized, open-label trial (IMpower110). Investigator-assessed median progression-free survival was 8.1 months in the atezolizumab arm compared with 5 months in the chemotherapy arm; the confirmed objective response rate was 38% versus 29%, respectively.

840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks for up to 1 year, unless there is disease recurrence or unacceptable toxicity. In a multicenter, randomized, open-label clinical trial (IMpower010), patients with stage IB to IIIA NSCLC who had complete tumor resection and received cisplatin-based adjuvant chemotherapy were randomized to treatment with atezolizumab or best supportive care (BSC). Treatment with atezolizumab significantly improved the primary endpoint of median disease-free survival (DFS) in stage II to IIIA NSCLC patients with PD-L1 expression in 1% or more of tumor cells compared with BSC (not reached vs. 35.3 months). In a prespecified secondary subgroup analysis of stage II to IIIA NSCLC patients with PD-L1 expression in 50% or more of tumor cells, median DFS was not reached versus 35.7 months, respectively; median DFS was 32.8 months versus 31.4 months, respectively, in an exploratory subgroup analysis of patients with PD-L1 expression in 1% to 49% of tumor cells.

840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity. Administer in combination with carboplatin (AUC 5 IV on day 1) and etoposide (100 mg/m2 IV on days 1, 2, and 3), every 3 weeks for 4 cycles. Administer atezolizumab prior to chemotherapy when given on the same day. In a randomized, double-blind, phase 3 clinical trial (IMpower133), the addition of atezolizumab to carboplatin plus etoposide significantly improved overall survival (12.3 months vs. 10.3 months) and progression-free survival (5.2 months vs. 4.3 months) compared with placebo plus carboplatin/etoposide. Survival at 1 year was 51.7% versus 38.2%, respectively. Treatment was well-tolerated, with 56.5% of patients in the atezolizumab arm experiencing grade 3 or 4 adverse reactions compared with 56.1% of those in the placebo arm. Immune-related adverse reactions occurred in 39.9% versus 24.5% of patients, respectively.[63611]

840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks. Administer in combination with bevacizumab 15 mg/kg IV every 3 weeks until disease progression or unacceptable toxicity. Administer atezolizumab prior to bevacizumab when given on the same day. In a multicenter, randomized, open-label clinical trial (IMbrave150), treatment with atezolizumab followed by bevacizumab significantly improved overall survival (not estimable vs. 13.2 months) and progression-free survival (6.8 months vs. 4.3 months) compared with sorafenib in patients with unresectable or metastatic HCC who have not received prior systemic therapy. The overall response rate was also significantly improved for patients treated with bevacizumab/atezolizumab by both RECIST1.1 criteria (28% vs. 12%; complete response [CR], 7% vs. 0%) and mRECIST criteria (33% vs. 13%; CR, 11% vs. 1.8%); the median duration of response was not estimable versus 6.3 months, respectively.

840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks, starting on cycle 2 (28 days after starting cobimetinib and vemurafenib therapy). Administer in combination with cobimetinib (60 mg orally once daily on days 1 to 21, every 28 days) and vemurafenib (720 mg orally twice daily). Cycle 1 consists of cobimetinib and vemurafenib only given as follows: cobimetinib 60 mg orally once daily on days 1 to 21 and vemurafenib 960 mg orally twice daily on days 1 to 21 and then 720 mg orally twice daily on days 22 to 28. At a median follow-up time of 18.9 months, the investigator-assessed median progression-free survival (PFS) time was significantly longer in patients who received atezolizumab, vemurafenib, and cobimetinib compared with placebo, vemurafenib, and cobimetinib (15.1 months vs. 10.6 months; hazard ratio (HR) = 0.78; 95% CI, 0.63 to 0.97) in an international, randomized, double-blind, placebo-controlled, phase 3 trial (n = 514; IMspire150 trial). When PFS was assessed by an independent review committee, the median PFS time was not significantly improved in the atezolizumab arm (16.1 months vs. 12.3 months; HR = 0.85; 95% CI, 0.67 to 1.07). Additionally, the median overall survival (OS) time was not significantly improved in patients who received atezolizumab compared with placebo (39 months vs. 25.8 months; HR = 0.84; 95% CI, 0.66 to 1.06) in an interim OS analysis of the IMspire150 trial performed at median follow-up times of 29.1 and 22.8 months, respectively. Patients (median age 54 years; range, 43 to 64 years) in this trial had BRAF V600 mutation-positive unresectable stage IIIc or stage IV melanoma and had not received previous systemic therapy for metastatic disease.

840 mg IV every 2 weeks; OR 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks until disease progression or unacceptable toxicity. The overall response rate was 24% (all partial responses) in 49 patients (median age, 31 years; range, 12 to 70 years) with unresectable or metastatic alveolar soft part sarcoma who received atezolizumab in a single-arm (ML39345) study. The duration of response lasted from 1 month to more than 41 months in responding patients; additionally, 67% and 42% of responding patients had a duration of response lasting at least 6 and 12 months, respectively.

15 mg/kg (maximum dose of 1,200 mg) every 3 weeks until disease progression or unacceptable toxicity. The efficacy of atezolizumab in pediatric patients is supported by evidence from a study in adults with alveolar soft part sarcoma (ASPS), 2 adolescent pediatric patients with metastatic ASPS, and pharmacokinetic and safety data in pediatric patients aged 2 to 16 years.

Dosage not established.

Dosage not established.

Dosage not established.

1,200 mg IV over 60 minutes on day 1, in combination with gemcitabine (1,000 mg/m2 IV on days 1 and 8) and cisplatin (70 mg/m2 IV on day 1), every 21 days for up to 6 cycles; may continue atezolizumab monotherapy after the completion of chemotherapy until disease progression or unacceptable toxicity. If the first atezolizumab infusion is tolerated, all subsequent infusions may be administered over 30 minutes. In a randomized phase 3 trial (the IMvigor 130 trial), the addition of atezolizumab to platinum-based chemotherapy in patients with metastatic urothelial cancer significantly improved progression-free survival (PFS) compared with platinum-based chemotherapy alone in the intent-to-treat population; the PFS benefit in the atezolizumab arm was seen across all subgroups, although it was not statistically significant in several including patients with PD-L1 0/1 expression and in patients receiving carboplatin- versus cisplatin-based regimens. At an interim analysis after 11.8 months of follow-up, overall survival was not significantly different between groups.

1,200 mg IV over 60 minutes on day 1, in combination with gemcitabine (1,000 mg/m2 IV on days 1 and 8) and carboplatin (AUC 4.5 IV on day 1), every 21 days for up to 6 cycles; may continue atezolizumab monotherapy after the completion of chemotherapy until disease progression or unacceptable toxicity. If the first atezolizumab infusion is tolerated, all subsequent infusions may be administered over 30 minutes. In a randomized phase 3 trial (the IMvigor 130 trial), the addition of atezolizumab to platinum-based chemotherapy in patients with metastatic urothelial cancer significantly improved progression-free survival (PFS) compared with platinum-based chemotherapy alone in the intent-to-treat population; the PFS benefit in the atezolizumab arm was seen across all subgroups, although it was not statistically significant in several including patients with PD-L1 0/1 expression and in patients receiving carboplatin- versus cisplatin-based regimens. At an interim analysis after 11.8 months of follow-up, overall survival was not significantly different between groups.

1,200 mg IV over 60 minutes plus bevacizumab (15 mg/kg IV over 90 minutes), repeated every 3 weeks until disease progression or unacceptable toxicity. If the first atezolizumab infusion is tolerated over 60 minutes, all subsequent infusions may be infused over 30 minutes. If the first bevacizumab infusion is tolerated over 90 minutes, the second infusion may be given over 60 minutes and if well-tolerated, subsequent bevacizumab infusions may be given over 30 minutes. In a randomized, phase 3 clinical trial, first-line treatment with atezolizumab plus bevacizumab significantly improved median investigator-assessed PFS in patients with advanced or metastatic RCC compared with sunitinib; however, these results were not supported by an independent review committee (IRC) which found a nonsignificant trend toward improved PFS. An exploratory analysis found that treatment with atezolizumab plus bevacizumab significantly improved investigator-assessed PFS in intent-to-treat patients with sarcamoid histology, which has a particularly poor prognosis. Treatment with atezolizumab plus bevacizumab did not significantly improve overall survival compared with sunitinib in this patient population, but patients who received combination therapy experienced a longer time to clinically relevant decline.

Dosage not established.

840 mg IV every 2 weeks in combination with nab-paclitaxel (125 mg/m2 once weekly) for 12 weeks, followed by atezolizumab 840 mg IV every 2 weeks in combination with doxorubicin (60 mg/m2 IV) plus cyclophosphamide (600 mg/m2 IV every 2 weeks) for 8 weeks (dose-dense AC), followed by surgery. After surgery, continue atezolizumab 1,200 mg IV every 3 weeks for 11 cycles to complete approximately 12 months of atezolizumab therapy. In a randomized, phase 3 clinical trial (IMpassion031), neoadjuvant treatment with atezolizumab plus sequential nab-paclitaxel and AC chemotherapy significantly improved pCR compared with neoadjuvant placebo plus sequential nab-paclitaxel and AC chemotherapy in patients with early TNBC, regardless of PD-L1 status.

†Indicates off-label use

Treatment-Related Immune-Mediated HepatitisNo Tumor Involvement of the LiverAST or ALT level of more than 3 to 8 times the ULN or a total bilirubin level of more than 1.5 to 3 times the ULN: Hold atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue atezolizumab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids. AST or ALT level more than 8 times the ULN or a total bilirubin level more than 3-times the ULN: Permanently discontinue atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).Tumor Involvement of the LiverBaseline AST or ALT level at the ULN or less: Hold or permanently discontinue atezolizumab based on recommendations for hepatitis with no tumor involvement of the liver.Baseline AST or ALT level of more than 1 to 3 times the ULNAST or ALT level of more than 5 to 10 times the ULN: Hold atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue atezolizumab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids. Baseline AST or ALT level of more than 3 to 5 times the ULNAST or ALT level of more than 8 to 10 times the ULN: Hold atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue atezolizumab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids. Any Baseline AST or ALT levelAST or ALT level more than 10 times the ULN or a total bilirubin level to more than 3 times the ULN: Permanently discontinue atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).

Treatment-Related Immune-Mediated Nephritis with Renal Dysfunction Grade 2 or 3 increased serum creatinine (SCr) level: Hold atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper). Resume therapy when the adverse event recovers to grade 1 or less after the corticosteroid taper. Permanently discontinue atezolizumab in patients who do not have a complete or partial resolution of toxicity or who cannot reduce their daily prednisone dose to less than 10 mg (or equivalent) within 12 weeks of initiating steroids. Grade 4 increased SCr level: Permanently discontinue atezolizumab and administer corticosteroids (i.e., prednisone 1 to 2 mg/kg per day or equivalent, followed by a 1-month taper starting when the toxicity resolves to grade 1 or less).

Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.

Tecentriq Intravenous Inj Sol: 1mL, 60mg

840 mg IV every 2 weeks; 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks.

840 mg IV every 2 weeks; 1,200 mg IV every 3 weeks; OR 1,680 mg IV every 4 weeks.

15 mg/kg (maximum of 1,200 mg) IV every 3 weeks.

2 years and older: 15 mg/kg (maximum of 1,200 mg) IV every 3 weeks.1 year: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Atezolizumab is an Fc-engineered, humanized, non-glycosylated IgG1 kappa monoclonal antibody that inhibits programmed death ligand 1 (PD-L1) interactions with the PD-1 and B7.1 receptors. PD-L1 may be expressed on tumor cells and/or tumor-infiltrating immune cells, and can contribute to inhibition of the anti-tumor immune response in the tumor microenvironment; PD-1 and B7.1 receptors are found on T-cells and antigen-presenting cells. The PD-1 pathway regulates the balance between T-cell activation and protection of healthy tissues from immune-mediated damage. In cancer, the PD-1 pathway is thought to play an important role in the interaction of tumor cells with the host immune response. Binding of PD-L1 to the PD-1 and B7.1 receptors suppresses cytotoxic T-cell activity, T-cell proliferation, and cytokine production; PD-L1 expression in a tumor cell may provide adaptive immune resistance and lead to poor outcomes. Atezolizumab binds to PD-L1 and prevents its interaction with both PD-1 and B7.1 receptors, releasing the PD-L1/PD-1 mediated inhibition of an anti-tumor immune response without inducing antibody-dependent cellular cytotoxicity. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.

Atezolizumab is administered intravenously. Exposure to atezolizumab increases in a dose-proportional manner over a range of 1 mg/kg to 20 mg/kg, including the recommended fixed dose of 1,200 mg. Clearance was 0.2 L/day (CV, 29%) and volume of distribution (Vd) at steady-state was 6.9 L. Atezolizumab clearance was found to decrease over time, with a mean maximal reduction (% coefficient of variation; CV%) from baseline value of 17% (CV%, 41%); however, this was not considered statistically relevant. The terminal half-life was 27 days, with steady-state reached after 6 to 9 weeks following multiple doses.[60793]

The systemic accumulation ratio for atezolizumab was 3.3-fold when administered every 2 weeks and 1.9-fold when administered every 3 weeks.

Based on its mechanism of action, atezolizumab may cause fetal harm if used during pregnancy. Atezolizumab is an immunoglobulin G1 antibody and may cross the placental barrier. Fetal exposure to atezolizumab may increase the risk of developing immune-mediated disorders or altering the normal immune response. Advise women of reproductive potential of the risk to a fetus. The PD-1 pathway is associated with decidual CD8-positive T-cell function and the PD1/PD-L1 interaction may be important in maintaining fetal tolerance during pregnancy. PD1/PDL1 Inhibitors, such as atezolizumab, may impair maternal immune tolerance resulting in spontaneous abortion, intrauterine growth restriction, or early-onset preeclampsia.    

Due to the potential for serious adverse reactions in breastfed children, the manufacturer recommends that patients avoid breast-feeding during atezolizumab therapy and for 5 months after the final dose. It is not known if atezolizumab is present in human milk or if it has effects on the breastfed child or on milk production. Use atezolizumab with caution during breastfeeding, especially while nursing a newborn or preterm infant. Because atezolizumab is a large protein molecule (molecular weight of 145,000 Daltons), the amount of drug in milk is likely to be very low. It may also be partially destroyed in the gastrointestinal tract resulting in minimal absorption.