Tecentriq

Tecentriq

atezolizumab

Manufacturer:

Roche

Distributor:

DKSH
Full Prescribing Info
Contents
Atezolizumab.
Description
Tecentriq is supplied as a single-use vial containing 20 ml preservative-free, colorless to slightly yellow solution, at a concentration of 60 mg/ml as follows: 20 mL vial containing a total of 1,200 mg atezolizumab.
Sterile/Radioactive Statement: Sterile product.
Excipients/Inactive Ingredients: as registered locally.
Action
Pharmacotherapeutic group: Anti-neoplastic agent, humanized immunoglobulin G1 (IgG1) monoclonal antibody. ATC code: L01XC32.
Pharmacology:
Pharmacodynamics: Mechanism of Action: Binding of PD-L1 to the PD-1 and B7.1 receptors found on T cells suppresses cytotoxic T-cell activity through the inhibition of T-cell proliferation and cytokine production. PD-L1 may be expressed on tumor cells and tumor-infiltrating immune cells, and can contribute to the inhibition of the anti-tumor immune response in the microenvironment.
Atezolizumab is an Fc-engineered humanized immunoglobulin G1 (IgG1) monoclonal antibody that directly binds to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors, releasing PD-L1/PD-1 pathway-mediated inhibition of the immune response, including reactivating the anti-tumor immune response. Atezolizumab leaves the PD-L2/PD-1 interaction intact. In syngeneic mouse tumor models, blocking PD-L1 activity resulted in decreased tumor growth.
Clinical/Efficacy Studies: UC: IMvigor 211: A phase III, open-label, multi center, international, randomized study, GO29294 (IMvigor211), was conducted to evaluate the efficacy and safety of Tecentriq compared with chemotherapy (investigator's choice of vinflunine, docetaxel, or paclitaxel) in patients with locally advanced or metastatic urothelial carcinoma who progressed during or following a platinum-containing regimen. This study excluded patients who had a history of autoimmune disease; active or corticosteroid-dependent brain metastases; administration of a live, attenuated vaccine within 28 days prior to enrollment; and administration of systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medicinal product within 2 weeks prior to enrollment. Tumor assessments were conducted every 9 weeks for the first 54 weeks, and every 12 weeks thereafter. Tumor specimens were evaluated prospectively for PD-L1 expression on tumour-infiltrating immune cells (IC) and the results were used to define the PD-L1 expression subgroups for the analyses described as follows.
A total of 931 patients were enrolled. Patients were randomized (1:1) to receive either Tecentriq or chemotherapy. Randomization was stratified by chemotherapy (vinflunine vs taxane), PD-L1 expression status on IC (< 5% vs ≥ 5%), number of prognostic risk factors (0 vs. 1-3), and liver metastases (yes vs. no). Prognostic risk factors included time from prior chemotherapy of < 3 months, ECOG performance status > 0 and hemoglobin < 10 g/dL.
Tecentriq was administered as a fixed dose of 1200 mg by intravenous infusion every 3 weeks. No dose reduction of Tecentriq was allowed. Patients were treated until loss of clinical benefit as assessed by the investigator or unacceptable toxicity. Vinflunine was administered 320 mg/m2 by intravenous infusion on day 1 of each 3-week cycle until disease progression or unacceptable toxicity. Paclitaxel was administered 175 mg/m2 by intravenous infusion over 3 hours on day 1 of each 3-week cycle until disease progression or unacceptable toxicity. Docetaxel was administered 75 mg/m2 by intravenous infusion on day 1 of each 3-week cycle until disease progression or unacceptable toxicity. For all treated patients, the median duration of treatment was 2.8 months for the Tecentriq arm, 2.1 months for the vinflunine and paclitaxel arms and 1.6 months for the docetaxel arm.
The demographic and baseline disease characteristics of the primary analysis population were well balanced between the treatment arms. The median age was 67 years (range: 31 to 88), and 77.1% of patients were male. The majority of patients were white (72.1%), 53.9% of patients within the chemotherapy arm received vinflunine, 71.4% of patients had at least one poor prognostic risk factor and 28.8% had liver metastases at baseline. Baseline ECOG performance status was 0 (45.6%) or 1 (54.4%). Bladder was the primary tumor site for 71.1% of patients and 25.4% of patients had upper tract urothelial carcinoma. There were 24.2% of patients who received only prior platinum-containing adjuvant or neoadjuvant therapy and progressed within 12 months.
The primary efficacy endpoint for IMvigor211 was overall survival (OS). Secondary efficacy endpoints were objective response rate (ORR), progression-free survival (PFS), and duration of response (DOR). OS comparisons between the treatment arm and control arm were tested using a hierarchical fixed-sequence procedure based on a stratified log-rank test at two-sided level of 5% as follows: step 1) PD-L1 expression ≥5% subgroup, step 2) PD-L1 expression ≥1% subgroup, step 3) all comers. OS results for each of steps 2 and 3 could only be formally tested if the result in the preceding step was statistically significant.
The median survival follow up was 17 months. Study IMvigor211 did not meet its primary endpoint. In the subset of patients with tumors having PD-L1 expression ≥5%, Tecentriq did not demonstrate a statistically significant survival benefit compared to chemotherapy with an OS HR of 0.87 (95% CI: 0.63, 1.21; median OS of 11.1 vs. 10.6 months for Tecentriq and chemotherapy respectively). The stratified log rank p value was 0.41. As a consequence, no formal statistical testing was performed for OS in the PD-L1 expression ≥1% subgroup or in all comers, and results of those analyses are considered exploratory. The key results in the all comer population are summarised in Table 1. The Kaplan Meier curve for OS in the all comer population is presented in Figure 1. (See Table 1 and Figure 1.)

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IMvigor 210: A phase II, multi-center, international, two-cohort, single-arm clinical trial, GO29293 (IMvigor210), was conducted in patients with locally advanced or metastatic urothelial carcinoma (also known as urothelial bladder cancer). The study enrolled a total of 438 patients and had two patient cohorts. Cohort 1 included previously untreated patients with locally advanced or metastatic urothelial carcinoma who were ineligible or unfit for cisplatin-based chemotherapy or had disease progression at least 12 months after treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen. Cohort 2 included patients who received at least one platinum-based chemotherapy regimen for locally advanced or metastatic urothelial carcinoma or had disease progression within 12 months of treatment with a platinum-containing neoadjuvant or adjuvant chemotherapy regimen.
In cohort 1, 119 patients were treated with Tecentriq 1200 mg by intraveneous infusion every 3 weeks until disease progression. The median age was 73 years. Most patients were male (81%), and the majority of patients were white (91%).
Cohort 1, included 45 patients (38%) with ECOG performance status of 0, 50 patients (42%) with ECOG performances status of 1 and 24 patients (20%) with ECOG performance status of 2, 35 patients (29%) with no Bajorin risk factors (ECOG performance status ≥2 and visceral metastasis), 66 patients (56%) with one Bajorin risk factor and 18 patients (15%) with two Bajorin risk factors 84 patients (71%) with impaired renal function (GFR < 60 ml/min), and 25 patients (21%) with liver metastasis.
The primary efficacy endpoint for Cohort 1 was confirmed objective response rate (ORR) as assessed by an independent review facility (IRF) using RECIST v1.1. The primary analysis was performed when all patients had at least 24 weeks of follow-up. Median duration of treatment was 15.0 weeks and median duration of survival follow-up was 8.5 months in all comers. Clinically relevant IRF-assessed ORRs per RECIST v1.1 were shown; however, when compared to a prespecified historical control response rate of 10%, statistical significance was not reached for the primary endpoint. The confirmed ORRs per IRF-RECIST v1.1 were 21.9% (95% CI: 9.3, 40.0) in patients with PD-L1 expression ≥ 5%, 18.8% (95% CI: 10.9, 29.0) in patients with PD-L1 expression ≥ 1%, and 19.3% (95% CI: 12.7, 27.6) in all comers. The median duration of response (DOR) was not reached in any PD-L1 expression subgroup or in all comers. OS was not mature with an event ratio of approximately 40%. Median OS for all patient subgroups (PD-L1 expression ≥ 5% and ≥ 1%) and in all comers was 10.6 months.
An updated analysis was performed with a median duration of survival follow up of 17.2 months for Cohort 1 and is summarized in Table 2. The median DOR was not reached in any PD-L1 expression subgroup or in all comers. (See Table 2.)

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In Cohort 2, the co-primary efficacy endpoints were confirmed ORR as assessed by an IRF using RECIST v1.1 and investigator-assessed ORR according to Modified RECIST (mRECIST) criteria. There were 310 patients treated with Tecentriq 1200 mg by intravenous infusion every 3 weeks until loss of clinical benefit. The primary analysis of Cohort 2 was performed when all patients had at least 24 weeks of follow-up. The study met its co-primary endpoints in all subgroups in Cohort 2, demonstrating statistically significant ORRs per IRF-assessed RECIST v1.1 and investigator-assessed mRECIST compared to a prespecified historical control response rate of 10%.
An analysis was also performed with a median duration of survival follow up 21.1 months for Cohort 2. The confirmed ORRs per IRF-RECIST v1.1 were 28.0% (95% CI: 19.5, 37.9) in patients with PD-L1 expression ≥ 5%, 19.3% (95% CI: 14.2, 25.4) in patients with PD-L1 expression ≥ 1%, and 15.8% (95% CI: 11.9, 20.4) in all comers. The confirmed ORR per investigator-assessed mRECIST was 29.0% (95% CI: 20.4, 38.9) in patients with PD-L1 expression ≥ 5%, 23.7% (95% CI: 18.1, 30.1) in patients with PD-L1 expression ≥ 1%, and 19.7% (95% CI: 15.4, 24.6) in all comers. The rate of complete response per IRF-RECIST v1.1 in the all comer population was 6.1% (95% CI: 3.7, 9.4) Median DOR was not reached in any PD-L1 expression subgroups or in all comers, however was reached in patients with PD-L1 expression <1% (13.3 months; 95% CI 4.2, NE). The OS rate at 12 months was 37% in all comers.
NSCLC: 1L non-squamous NSCLC: IMpower 150: A phase III, open-label, randomized study, GO29436 (IMpower150), was conducted to evaluate the efficacy and safety of Tecentriq in combination with paclitaxel and carboplatin, with or without bevacizumab, in chemotherapy-naïve patients with metastatic non-squamous NSCLC. A total of 1202 patients were enrolled and were randomized in a 1:1:1 ratio to receive one of the treatment regimens described in Table 3. Randomization was stratified by sex, presence of liver metastases and PD-L1 tumor expression on tumor cells (TC) and tumor infiltrating cells (IC). (See Table 3.)

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Patients were excluded if they had history of autoimmune disease; administration of a live, attenuated vaccine within 28 days prior to randomization; administration of systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to randomization; active or untreated CNS metastases; clear tumor infiltration into the thoracic great vessels or clear cavitation of pulmonary lesions, as seen on imaging. Tumor assessments were conducted every 6 weeks for the first 48 weeks following Cycle 1, Day 1 and then every 9 weeks thereafter.
The demographics and baseline disease characteristics of the study population were well balanced between the treatment arms. In this study, the median age was 63 years (range: 31 to 90), and 60% of patients were male. The majority of patients were white (82%). Approximately 10% of patients had known EGFR mutations, 4% had known ALK rearrangements, 14% had liver metastases at baseline, and most patients were current or previous smokers (80%). Baseline ECOG performance status was 0 (43%) or 1 (57%).
At the time of the final analysis for PFS, patients had a median follow up time of 15.3 months. The ITT population included patients with EGFR mutations or ALK rearrangements who should have been previously treated with tyrosine kinase inhibitors, demonstrated PFS improvement in Arm B as compared to Arm C (HR: 0.61 [95% CI: 0.52, 0.72] median PFS 8.3 vs 6.8 months).
At the time of the interim OS analysis, patients had a median follow up time of 19.7 months. The key results from this analysis are summarized in Table 4. Kaplan-Meier curves for OS in the ITT population are presented in Figure 2. Figure 3 summarizes the results of OS in the ITT and PD-L1 subgroups, demonstrating OS benefit with Tecentriq in all subgroups, including those with PD-L1 expression <1% on TC and IC. Updated PFS results are also demonstrated in Figure 4 and 5. (See Table 4, Figures 2, 3, 4 and 5.)

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Pre-specified subgroup analyses from the interim OS analysis showed numerical OS improvements in the Tecentriq with bevacizumab, paclitaxel, carboplatin arm as compared to the bevacizumab, paclitaxel and carboplatin arm for patients with EGFR mutations or ALK rearrangements (HR: 0.54 [95% CI: 0.29, 1.03], median OS NE vs. 17.5 months) and liver metastases (HR:0.52 [95% CI: 0.33, 0.82], median OS 13.3 vs 9.4 months). Numerical PFS improvements were also shown in patients with EGFR mutations or ALK rearrangements (HR: 0.55 [95% CI 0.34, 0.90], median PFS 10 vs. 6.1 months) and liver metastases (HR: 0.41 [95%CI 0.26, 0.62], median PFS 8.2 vs. 5.4 months).
This study also evaluated Physical Function and Patient-Reported Treatment-Related Symptoms using the EORTC QLQ-C30 and EORTC QLQ-LC13 measures at the time of the final PFS analysis. On average, patients who received Tecentriq with bevacizumab, paclitaxel and carboplatin reported minimal treatment burden as indicated by minimal deterioration in both Physical Function and Patient-Reported Treatment-Related Symptom Scores (i.e. fatigue, constipation, diarrhea, nausea/vomiting, hemoptysis, dysphagia, and sore mouth) while on treatment. Average patient-reported physical function and treatment-related symptom scores in both patients who received Tecentriq with bevacizumab, paclitaxel and carboplatin as well as patients who received bevacizumab in combination with paclitaxel and carboplatin, were comparable while on treatment.
IMpower130: A Phase III, open-label, randomized study, GO29537 (IMpower130) was conducted to evaluate the efficacy and safety of Tecentriq in combination with nab-paclitaxel and carboplatin, in chemotherapy-naïve patients with metastatic non-squamous NSCLC. Patients including those with EGFR or ALK genomic tumor aberrations, were enrolled and were randomized in a 2:1 ratio to receive one of the treatment regimens described in Table 5. Randomization was stratified by sex, presence of liver metastases and PD-L1 tumor expression on tumor cells (TC) and tumor infiltrating cells (IC). Patients in treatment regimen B were able to crossover and receive Tecentriq monotherapy following disease progression. (See Table 5.)

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Patients were excluded if they had history of autoimmune disease, administration of live, attenuated vaccine within 28 days prior to randomization, administration of immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to randomization, and active or untreated CNS metastases. Tumor assessments were conducted every 6 weeks for the first 48 weeks following Cycle 1, then every 9 weeks thereafter.
The demographics and baseline disease characteristics of the study population (n = 723) were well balanced between the treatment arms. The median age was 64 years (range 18 to 86). The majority of the patients were, male (57%), white (90%). 14.8% of patients had liver metastases at baseline, and most patients were current or previous smokers (88%). The majority of patients had baseline ECOG performance status of 1 (58.7%).
The primary analysis was conducted in all patients, excluding those with EGFR or ALK genomic tumor aberrations (n = 679). Patients had a median survival follow up time of 18.6 months. Improvements in OS and PFS were demonstrated with Tecentriq + nab-paclitaxel + carboplatin compared to the control. The key results are summarized in Table 6 and Kaplan-Meier curves for OS and PFS are presented in Figures 1 and 3, respectively.
All PD-L1 subgroups, regardless of expression, derived benefit in terms of OS and PFS; the results are summarized in Figure 2 and 4. Consistent OS and PFS benefit was demonstrated in all other pre-specified subgroups, with the exception of patients with liver metastases who did not show improved OS with Tecentriq, nab-paclitaxel and carboplatin, compared to nab-paclitaxel and carboplatin (HR of 1.04, 95% CI: 0.63,1.72).
Approximately 66% of patients in the nab-paclitaxel and carboplatin arm received any anti-cancer therapy after disease progression compared to 39% in the Tecentriq, nab-paclitaxel and carboplatin arm. These included, approximately 59% of patients in the nab-paclitaxel and carboplatin arm received any cancer immunotherapy after disease progression, which includes Tecentriq as crossover (41% of all patients), compared to 7.3% in the Tecentriq, nab-paclitaxel and carboplatin arm. (See Table 6, Figures 6, 7, 8 and 9.)

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The study also evaluated Physical Function and Patient Reported Treatment-Related Symptoms using the EORTC QLQ-C30 and EORTC QLQ-LC13 measures. On average, patients who received Tecentriq with nab-paclitaxel and carboplatin reported high functioning and no clinically meaningful worsening in treatment-related symptoms. There was no difference in delay of lung-related symptoms (dyspnea, cough and chest pain) however patients receiving Tecentriq, nab-paclitaxel and carboplatin reported less worsening of these symptoms over time.
1L ES - SCLC: IMpower133: A Phase I/III, randomized, multicenter, double-blind, placebo controlled study, GO30081 (IMpower133), was conducted to evaluate the efficacy and safety of Tecentriq in combination with carboplatin and etoposide in patients with chemotherapy-naïve ES-SCLC. A total of 403 patients were randomized (1:1) to receive one of the treatment regimens described in Table 5. Randomization was stratified by sex, ECOG performance status, and presence of brain metastases.
This study excluded patients who had active or untreated CNS metastases; history of autoimmune disease; administration of live, attenuated vaccine within 4 weeks prior to randomization; administration of systemic immunosuppressive medications within 1 week prior to randomization. Tumor assessments were conducted every 6 weeks for the first 48 weeks following Cycle 1, Day 1 and then every 9 weeks thereafter. Patients treated beyond disease progression had tumor assessment conducted every 6 weeks until treatment discontinuation. (See Table 7.)

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The demographic and baseline disease characteristics of the primary analysis population were well balanced between the treatment arms. The median age was 64 years (range: 26 to 90 years). The majority of patients were male (65%), white (80%), and 9% had brain metastases and most patients were current or previous smokers (97%). Baseline ECOG performance status was 0 (35%) or 1 (65%).
At the time of the primary analysis, patients had a median survival follow up time of 13.9 months. The key results are summarized in Table 6. Kaplan-Meier curves for OS and PFS are presented in Figure 6 and 7. (See Table 8, Figures 10 and 11.)

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This study also included an exploratory analysis of average score changes from baseline in patient-reported symptoms, physical function, and health-related quality of life (measured using the EORTC QLC-C30 and QLC-LC13). On average, patients who received Tecentriq with carboplatin and etoposide reported early and notable improvements in lung cancer-related symptoms (e.g., coughing, chest pain, dyspnea) and physical function. Changes in treatment-related symptoms (e.g., diarrhea, nausea and vomiting, sore mouth, peripheral neuropathy) were comparable between arms throughout induction and most visits through week 54. Overall, patients treated with Tecentriq, carboplatin and etoposide achieved more pronounced and enduring improvements in health-related quality of life (≥10-point score increases at most visits through Week 48) compared to patients treated with placebo, carboplatin and etoposide, who reported nominal improvements (<10-point score increases) at most study treatment visits.
2L NSCLC: OAK: A phase III, open-label, multi-center, international, randomized study, GO28915 (OAK), was conducted to evaluate the efficacy and safety of Tecentriq compared with docetaxel in patients with locally advanced or metastatic NSCLC who have progressed during or following a platinum-containing regimen. A total of 1225 patients were enrolled, with the primary analysis population consisting of the first 850 randomized patients. Eligible patients were stratified by PD-L1 expression status in tumor-infiltrating immune cells (IC), by the number of prior chemotherapy regimens, and by histology. Patients were randomized (1:1) to receive either Tecentriq or docetaxel. This study excluded patients who had a history of autoimmune disease, active or corticosteroid-dependent brain metastases, administration of a live, attenuated vaccine within 28 days prior to enrollment, administration of systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to enrollment. Tumor assessments were conducted every 6 weeks for the first 36 weeks, and every 9 weeks thereafter. Tumor specimens were evaluated prospectively for PD-L1 expression on tumor cells (TC) and IC and the results were used to define the PD-L1 expression subgroups for the analyses described as follows.
The demographic and baseline disease characteristics of the primary analysis population were well balanced between the treatment arms. The median age was 64 years (range: 33 to 85), and 61% of patients were male. The majority of patients were white (70%). Approximately three-fourths of patients had non-squamous disease (74%), 10% had known EGFR mutation, 0.2% had known ALK rearrangements, 10% had CNS metastases at baseline, and most patients were current or previous smokers (82%). Baseline ECOG performance status was 0 (37%) or 1 (63%). Seventy-five percent of patients received only one prior platinum-based therapeutic regimen.
Tecentriq was administered as a fixed dose of 1200 mg by IV infusion every 3 weeks. No dose reduction was allowed. Patients were treated until loss of clinical benefit as assessed by the investigator. Docetaxel was administered 75 mg/m2 by IV infusion on day 1 of each 21 day cycle until disease progression. For all treated patients, the median duration of treatment was 2.1 months for the docetaxel arm and 3.4 months for the Tecentriq arm.
The primary efficacy endpoint was OS. The key results of this study with a median survival follow-up of 21 months are summarized in Table 7. Kaplan-Meier curves for OS in the ITT population are presented in Figure 8. Figure 9 summarizes the results of OS in the ITT and PD-L1 subgroups, demonstrating OS benefit with Tecentriq in all subgroups, including those with PD-L1 expression < 1% in TC and IC. (See Table 9, Figures 12 and 13.)

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An improvement in OS was observed with Tecentriq compared to docetaxel in both non-squamous NSCLC patients (hazard ratio [HR] of 0.73, 95% CI: 0.60, 0.89; median OS of 15.6 vs. 11.2 months for Tecentriq and docetaxel, respectively) and squamous NSCLC patients (HR of 0.73, 95% CI: 0.54, 0.98; median OS of 8.9 vs. 7.7 months for Tecentriq and docetaxel, respectively). The observed OS improvement was consistently demonstrated across subgroups of patients including those with brain metastases at baseline (HR of 0.54, 95% CI: 0.31, 0.94; median OS of 20.1 vs. 11.9 months for Tecentriq and docetaxel respectively) and patients who were never smokers (HR of 0.71, 95% CI: 0.47, 1.08; median OS of 16.3 vs. 12.6 months for Tecentriq and docetaxel, respectively). However, patients with EGFR mutations did not show improved OS with Tecentriq compared to docetaxel (HR of 1.24, 95% CI: 0.71, 2.18; median OS of 10.5 vs. 16.2 months for Tecentriq and docetaxel respectively).
Prolonged time to deterioration of patient-reported pain in chest as measured by the EORTC QLQ-LC13 was observed with Tecentriq compared with docetaxel (HR 0.71, 95% CI: 0.49, 1.05; median not reached in either arm). The time to deterioration in other lung cancer symptoms (i.e. cough, dyspnea, and arm/shoulder pain) as measured by the EORTC QLQ-LC13 was similar between Tecentriq and docetaxel. The average global health status and functioning scores (i.e. physical, role, social, emotional, and cognitive) as measured by the EORTC QLQ-C30 did not show clinically meaningful deterioration over time for both treatment groups, suggesting maintained health-related quality of life and patient-reported functioning for patients remaining on treatment.
POPLAR: A phase II, multi-center, international, randomized, open-label, controlled study GO28753 (POPLAR), was conducted in patients with locally advanced or metastatic NSCLC. The primary efficacy outcome was overall survival. A total of 287 patients were randomized 1:1 to receive either Tecentriq or docetaxel. Randomization was stratified by PD-L1 expression status in IC, by the number of prior chemotherapy regimens and by histology. An updated analysis with a total of 200 deaths observed and a median survival follow-up of 22 months showed a median OS of 12.6 months in patients treated with Tecentriq vs. 9.7 months in patients treated with docetaxel (HR of 0.69, 95% CI: 0.52, 0.92). ORR was 15.3% vs. 14.7% and median DOR was 18.6 months vs. 7.2 months for Tecentriq vs. docetaxel, respectively.
1L TNBC: IMpassion130: A phase III, double-blind, two-arm, randomized, placebo-controlled study, WO29522 (IMpassion130), was conducted to evaluate the efficacy and safety of Tecentriq in combination with nab-paclitaxel, in patients with unresectable locally advanced or metastatic TNBC who had not received prior chemotherapy for metastatic disease. A total of 902 patients were enrolled and stratified by presence of liver metastases, prior taxane treatment, and by PD L1 expression status in tumor-infiltrating immune cells (IC). Patients were randomized to receive Tecentriq (840 mg) or placebo IV infusions on Days 1 and 15 of every 28-day cycle, plus nab-paclitaxel (100 mg/m2) administered via IV infusion on Days 1, 8 and 15 of every 28-day cycle. Patients received treatment until radiographic disease progression per RECIST v1.1, or unacceptable toxicity. Treatment with Tecentriq could be continued when nab-paclitaxel was stopped due to unacceptable toxicity.
Patients were excluded if they had a history of autoimmune disease; administration of a live, attenuated vaccine within 4 weeks prior to randomization; administration of systemic immunostimulatory agents within 4 weeks or systemic immunosuppressive medications within 2 weeks prior to randomization; untreated or corticosteroid-dependent brain metastases. Tumor assessments were performed every 8 weeks (± 1 week) for the first 12 months after Cycle 1, day 1 and every 12 weeks (± 1 week) thereafter.
The demographic and baseline disease characteristics of the study population were well balanced between the treatment arms. Most patients were women (99.6%). Sixty-seven percent of patients were white (67.5%), 17.8% were Asian, 6.5% were Black or African American, and 4.4% were American Indian or Alaskan Native. The median age was 55 years (range: 20-86). Baseline ECOG performance status was 0 (58.4%) or 1 (41.3%). Overall, 41% of enrolled patients had PD-L1 expression ≥1%, 27% had liver metastases and 7% brain metastases at baseline. Approximately half the patients had received a taxane (51%) or anthracycline (54%) in the (neo)adjuvant setting. Patient demographics and baseline tumor disease in the PD-L1 expression ≥1% population were generally representative of the broader study population.
PFS, ORR and DOR results for patients with PD-L1 expression ≥1% with a median survival follow up of 13 months are summarized in Table 8 and Figure 10. In addition, PFS benefit was observed in subgroups.
An updated OS analysis was performed with a median follow-up of 18 months. OS results are presented in Table 8 and Figure 11. (See Table 10, Figures 14 and 15.)

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Patient-reported endpoints measured by the EORTC QLQ-C30 suggest that patients maintained their global health status/health-related quality of life (HRQoL), physical functioning, and role functioning while on treatment. No differences in the time to a ≥10-point deterioration in HRQoL (HR: 0.94; 95% CI: 0.69, 1.28), physical function (HR: 1.02; 95% CI: 0.76, 1.37), or role function (HR: 0.77; 95% CI: 0.57, 1.04) were observed between the two arms. Mean scores at baseline for HRQoL (67.5 Tecentriq and nab-paclitaxel vs. 65.0 placebo and nab-paclitaxel), physical function (82.7 vs. 79.4), and role function (73.6 vs. 71.7) were comparable between arms; as well as throughout the course of treatment. In both arms, HRQoL, physical function and role function remained stable during treatment, with no clinically meaningful changes (a ≥10 point difference from baseline mean score) observed.
Immunogenicity: As with all therapeutic proteins, there is the potential for immune response to atezolizumab. Across multiple phase III studies, 13.1% to 38.5% of patients developed treatment-emergent anti-drug antibodies (ADAs) ADA positivity appeared to have no clinically relevant impact on pharmacokinetics or safety. Although some variability was observed across the studies, overall, ADA positivity appeared to have no clinically relevant impact on 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 antibodies to Tecentriq with the incidence of antibodies to other products may be misleading.
Pharmacokinetics: The pharmacokinetics of atezolizumab have been characterized in patients in multiple clinical trials at doses of 0.01 mg/kg to 20 mg/kg and 1200 mg every 3 weeks, as well as 840 mg every 2 weeks. Exposure to atezolizumab increased dose proportionally over the dose range of 1 mg/kg to 20 mg/kg. A population analysis that included 472 patients described atezolizumab pharmacokinetics for the dose range of 1-20 mg/kg with a linear two-compartment disposition model with first-order elimination. Based on pharmacokinetic modelling, the overall exposure of atezolizumab administered at dose of 840 mg every 2 weeks, 1200 mg every 3 weeks and 1680 mg every 4 weeks are comparable. A population pharmacokinetic analysis suggests that steady state is obtained after 6 to 9 weeks after multiple dose. The maximum systemic accumulation ratio across dosing regimen is 3.3.
Based on an analysis of exposure, safety and efficacy data, the following factors have no clinically relevant effect: age (21-89 years), body weight, gender, positive ADA status, albumin levels, tumor burden, region or ethnicity, renal impairment, mild hepatic impairment, level of PD-L1 expression, or ECOG status.
Absorption: Tecentriq is administered as an IV infusion. There have been no studies performed with other routes of administration.
Distribution: A population pharmacokinetic analysis indicates that central compartment volume of distribution (V1) is 3.28 l and volume at steady state (Vss) is 6.91 l in the typical patient.
Metabolism: The metabolism of Tecentriq has not been directly studied. Antibodies are cleared principally by catabolism.
Elimination: A population pharmacokinetic analysis indicates that the clearance of atezolizumab is 0.200 l/day and the typical terminal elimination half-life (t½) is 27 days.
Pharmacokinetics in Special Populations: Pediatric Population: The pharmacokinetic results from one early-phase, multi-centre open-label study that was conducted in pediatric (<18 years, n=69) and young adult patients (18-30 years, n=18), show that the clearance and volume of distribution of atezolizumab were comparable between pediatric patients receiving 15 mg/kg and young adult patients receiving 1200 mg of atezolizumab every 3 weeks when normalized by body weight, with exposure trending lower in pediatric patients as body weight decreased. These differences were not associated with a decrease in atezolizumab concentrations below the therapeutic target exposure. Data for children <2 years is limited thus no definitive conclusions can be made.
Geriatric Population: No dedicated studies of Tecentriq have been conducted in geriatric patients. The effect of age on the pharmacokinetics of atezolizumab was assessed in a population pharmacokinetic analysis. Age was not identified as a significant covariate influencing atezolizumab pharmacokinetics based on patients of age range of 21-89 years (n=472), and median of 62 years of age. No clinically important difference was observed in the pharmacokinetics of atezolizumab among patients <65 years (n=274), patients between 65-75 years (n=152) and patients >75 years (n=46) (see Special Dosage Instructions under Dosage & Administration).
Renal impairment: No dedicated studies of Tecentriq have been conducted in patients with renal impairment. In the population pharmacokinetic analysis, no clinically important differences in the clearance of atezolizumab were found in patients with mild (eGFR 60 to 89 ml/min/1.73 m2; n=208) or moderate (eGFR 30 to 59 ml/min/1.73 m2; n=116) renal impairment compared to patients with normal (eGFR greater than or equal to 90 ml/min/1.73 m2; n=140) renal function. Only a few patients had severe renal impairment (eGFR 15 to 29 ml/min/1.73 m2; n=8) (see Special Dosage Instructions under Dosage & Administration).
Hepatic impairment: No dedicated studies of Tecentriq have been conducted in patients with hepatic impairment. In the population pharmacokinetic analysis, there were no clinically important differences in the clearance of atezolizumab between patients with mild hepatic impairment (bilirubin ≤ULN and AST > ULN or bilirubin > 1.0 to 1.5 × ULN and any AST, n=71) and normal hepatic function (bilirubin and AST≤ULN, n=401). No data are available in patients with either moderate (bilirubin >1.5 to 3.0 x ULN and any AST) or severe (bilirubin >3.0 x ULN and any AST) hepatic impairment. Hepatic impairment was defined by the National Cancer Institute (NCI) criteria of hepatic dysfunction (see Special Dosage Instructions under Dosage & Administration).
Toxicology: Nonclinical Safety: Carcinogenicity: No carcinogenicity studies have been conducted with Tecentriq.
Genotoxicity: No mutagenicity studies have been conducted with Tecentriq.
Impairment of Fertility: No fertility studies have been conducted with Tecentriq; however, assessment of the cynomolgus monkey male and female reproductive organs was included in the chronic toxicity study. Tecentriq had an effect on menstrual cycles in all female monkeys in the 50 mg/kg dose group characterized by an irregular cycle pattern during the dosing phase and correlated with the lack of fresh corpora lutea in the ovaries at the terminal necropsy; this effect was reversible during the dose-free recovery period. There was no effect on the male reproductive organs.
Reproductive Toxicity: No reproductive or teratogenicity studies in animals have been conducted with Tecentriq. The PD-L1/PD-1 signaling pathway is well established as essential in maternal / fetal tolerance and embryo-fetal survival during gestation. Administration of Tecentriq is expected to have an adverse effect on pregnancy and poses a risk to the human fetus, including embryo lethality.
Other: Not applicable.
Indications/Uses
Urothelial carcinoma: Tecentriq as monotherapy is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma (UC): after prior chemotherapy; or who are considered cisplatin ineligible and whose tumours have a PD-L1 expression ≥ 5%; or who are not eligible for any platinum-containing chemotherapy regardless of level of tumor PD-L1 expression.
Non-small cell lung cancer: Tecentriq, in combination with bevacizumab, paclitaxel and carboplatin, is indicated for the first-line treatment of patients with metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK genomic tumor aberrations.
Patients with EGFR or ALK genomic tumor aberrations should have disease progression on approved therapy for NSCLC harboring these aberrations prior to receiving Tecentriq.
Tecentriq, in combination with nab-paclitaxel and carboplatin, is indicated for first-line treatment of adult patients with metastatic non-squamous NSCLC who do not have EGFR or ALK genomic tumor aberrations.
Tecentriq as monotherapy is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy.
Small cell lung cancer: Tecentriq, in combination with carboplatin and etoposide, is indicated for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).
Triple-negative breast cancer: Tecentriq, in combination with nab-paclitaxel, is indicated for the treatment of patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors have PD-L1 expression ≥1%, and who have not received prior chemotherapy for metastatic disease.
Dosage/Direction for Use
General: Tecentriq must be administered as an IV infusion under the supervision of a qualified healthcare professional. Do not administer as an IV push or bolus.
Do not co-administer other medicinal products through the same infusion line.
Substitution by any other biological medicinal product requires the consent of the prescribing physician.
The initial dose of Tecentriq must be administered over 60 minutes. If the first infusion is tolerated, all subsequent infusions may be administered over 30 minutes.
The recommended dose of Tecentriq in monotherapy or combination therapy is: 840 mg administered by IV infusion every 2 weeks, or 1200 mg administered by IV infusion every 3 weeks, or 1680 mg administered by IV infusion every 4 weeks.
Tecentriq monotherapy: 1L cisplatin - ineligible mUC: Patients should be selected for treatment based on the tumor expression of PD-L1 confirmed by a validated test (see Pharmacology: Pharmacodynamics: Clinical/ Efficacy Studies under Actions).
Tecentriq combination therapy: For the use of Tecentriq in combination therapy, please also refer to the full prescribing information for the combination product. Tecentriq should be administered prior to the combination therapy if given on the same day.
1L non-squamous NSCLC: Tecentriq in combination with bevacizumab, paclitaxel, and carboplatin: During the induction phase, the recommended dose of Tecentriq is 1200 mg administered by intravenous (IV) infusion, followed by bevacizumab, paclitaxel, and then carboplatin every 3 weeks for four or six cycles.
The induction phase is followed by a maintenance phase without chemotherapy in which 1200 mg Tecentriq followed by bevacizumab, is administered by IV infusion every 3 weeks.
Tecentriq in combination with nab-paclitaxel and carboplatin: During the induction phase, Tecentriq is administered according to its dosing schedules by IV infusion, and nab-paclitaxel and carboplatin are administered every 3 weeks for four or six cycles. For each 21-day cycle, nab-paclitaxel and carboplatin are administered on day 1. In addition, nab-paclitaxel is administered on days 8 and 15.
The induction phase is followed by a maintenance phase without chemotherapy in which Tecentriq is administered according to its dosing schedule.
1L ES-SCLC: Tecentriq in combination with carboplatin and etoposide: During the induction phase, Tecentriq is administered according to its dosing schedules by IV infusion and carboplatin and etoposide are administered by IV infusion every three weeks for four cycles. Carboplatin and etoposide are administered on day 1 of each cycle, and etoposide is also administered on days 2 and 3.
The induction phase is followed by a maintenance phase without chemotherapy in which 1200 mg Tecentriq is administered by IV infusion every 3 weeks.
The induction phase is followed by a maintenance phase without chemotherapy in which Tecentriq is administered according to its dosing schedules by IV infusion.
1L TNBC: Tecentriq in combination with nab-paclitaxel: Tecentriq is administered according to its dosing schedules by IV infusion and 100 mg/m2 nab-paclitaxel is administered on days 1, 8 and 15 during each 28-day cycle.
Patients should be selected for treatment based on the tumor expression of PD-L1 confirmed by a validated test (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions).
Duration of treatment: Patients are treated with Tecentriq until loss of clinical benefit (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions) or unacceptable toxicity.
1L TNBC: Patients are treated with Tecentriq until disease progression or unacceptable toxicity. (See Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions.)
Delayed or missed doses: If a planned dose of Tecentriq is missed, it should be administered as soon as possible. The schedule of administration should be adjusted to maintain the appropriate interval between doses.
Dose modifications: No dose reductions of Tecentriq are recommended.
Dose modifications for immune-related adverse reactions: Recommendations for specific adverse drug reactions (see General under Precautions and Clinical Trials under Adverse Reactions) are presented in Table 11. (See Table 11.)

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For other immune-related reactions, based on the type and severity of the reaction, treatment with Tecentriq should be withheld for Grades 2 or 3 immune-related adverse reactions and corticosteroid therapy (1-2 mg/kg/day prednisone or equivalent) should be initiated. If symptoms improve to ≤ Grade 1, taper corticosteroids as clinically indicated. Treatment with Tecentriq may be resumed if the event improves to ≤ Grade 1 within 12 weeks, and corticosteroids have been reduced to ≤ 10 mg oral prednisone or equivalent per day.
Treatment with Tecentriq should be permanently discontinued for Grade 4 immune-related adverse reactions, or when unable to reduce corticosteroid dose to the equivalent of ≤ 10 mg prednisone per day within 12 weeks after onset
Special Dosage Instructions: Pediatric use: The safety and efficacy of Tecentriq in children and adolescents below 18 years of age have not been established (see Use in Children under Precautions and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Geriatric use: Based on a population pharmacokinetic analysis, no dose adjustment of Tecentriq is required in patients ≥ 65 years of age (see Use in Elderly under Precautions and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Renal impairment: Based on a population pharmacokinetic analysis, no dose adjustment is required in patients with renal impairment (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Hepatic impairment: Based on a population pharmacokinetic analysis, no dose adjustment is required for patients with mild hepatic impairment. There are no data on patients with moderate or severe hepatic impairment (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Overdosage
There is no information on overdose with Tecentriq.
Contraindications
Tecentriq is contraindicated in patients with a known hypersensitivity to atezolizumab or any of the excipients.
Special Precautions
General: In order to improve the traceability of biological medicinal products, the trade name and the batch number of the administered product should be clearly recorded (or stated) in the patient file.
Immune-related pneumonitis: Cases of pneumonitis, including fatal cases, have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of pneumonitis. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related hepatitis: Cases of hepatitis, some leading to fatal outcomes, have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of hepatitis. Monitor aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin prior to and periodically during treatment with Tecentriq. Consider appropriate management of patients with abnormal liver function tests (LFTs) at baseline. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related colitis: Cases of diarrhea or colitis have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of colitis. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related endocrinopathies: Hypothyroidism, hyperthyroidism, adrenal insufficiency, hypophysitis, and type 1 diabetes mellitus, including diabetic ketoacidosis, have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for clinical signs and symptoms of endocrinopathies. Monitor thyroid function prior to and periodically during treatment with Tecentriq. Consider appropriate management of patients with abnormal thyroid function tests at baseline. Patients with abnormal thyroid function tests who are asymptomatic may receive Tecentriq. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related meningoencephalitis: Meningoencephalitis has been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for clinical signs and symptoms of meningitis or encephalitis. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related neuropathies: Myasthenic syndrome/myasthenia gravis or Guillain-Barré syndrome, which may be life threatening, were observed in patients receiving Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for symptoms of motor and sensory neuropathy. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related pancreatitis: Pancreatitis, including increases in serum amylase and lipase levels, has been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be closely monitored for signs and symptoms that are suggestive of acute pancreatitis. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related myocarditis: Myocarditis has been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for signs and symptoms of myocarditis. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related myositis: Case of myositis, including fatal cases, have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for the signs and symptoms of myositis. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Immune-related nephritis: Nephritis has been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Patients should be monitored for changes in renal function. Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Infusion-related reactions: Infusion-related reactions (IRRs) have been observed in clinical trials with Tecentriq (see Clinical Trials under Adverse Reactions). Refer to Dosage and Administration for recommended dose modifications under Dosage & Administration.
Special populations: Patients with autoimmune disease were excluded from clinical trials with Tecentriq. In the absence of data, Tecentriq should be used with caution in patients with autoimmune disease, after assessment of the potential risk/benefit.
Embryo-fetal toxicity: Based on the mechanism of action, the use of Tecentriq may cause fetal harm. 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.
Pregnant women should be advised of the potential risk to the fetus. Women of childbearing potential should be advised to use highly effective contraception during treatment with Tecentriq and for 5 months after the last dose (see Females and Males of Reproductive Potential under Use in Pregnancy & Lactation and Pharmacology: Toxicology: Nonclinical Safety: Reproductive Toxicity under Actions).
Renal Impairment: See Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Hepatic Impairment: See Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions.
Females and Males of Reproductive Potential: Fertility: Based on animal studies, Tecentriq may impair fertility in females of reproductive potential while receiving treatment (see Pharmacology: Toxicology: Nonclinical Safety: Impairment of Fertility under Actions).
Contraception: Female patients of childbearing potential should use highly effective contraception and take active measures to avoid pregnancy while undergoing Tecentriq treatment and for at least 5 months after the last dose (see General under Precautions and Pharmacology: Toxicology: Nonclinical Safety: Reproductive Toxicity under Actions).
Labor and Delivery: The use of Tecentriq during labor and delivery has not been established.
Ability to Drive and Use Machines: No studies on the effects on the ability to drive and to use machines have been performed.
Use in Pregnancy: There are no clinical studies of Tecentriq in pregnant women. Tecentriq is not recommended during pregnancy unless the potential benefit for the mother outweighs the potential risk to the fetus (see Pharmacology: Toxicology: Nonclinical Safety: Reproductive Toxicity under Actions).
Use in Lactation: It is not known whether Tecentriq is excreted in human breast milk. No studies have been conducted to assess the impact of Tecentriq on milk production or its presence in breast milk. As the potential for harm to the nursing infant is unknown, a decision must be made to either discontinue breast-feeding or discontinue Tecentriq therapy.
Use in Children: Tecentriq is not approved for use in the patients under the age of 18 years. The safety and efficacy of Tecentriq in this population has not been established. Tecentriq did not demonstrate clinical benefit in pediatric patients in a clinical trial. (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Use in Elderly: No overall differences in safety or efficacy were observed between patients ≥ 65 years of age and younger patients (see Special Dosage Instructions under Dosage & Administration and Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
Use In Pregnancy & Lactation
Pregnancy: There are no clinical studies of Tecentriq in pregnant women. Tecentriq is not recommended during pregnancy unless the potential benefit for the mother outweighs the potential risk to the fetus (see Pharmacology: Toxicology: Nonclinical Safety: Reproductive Toxicity under Actions).
Labor and Delivery: The use of Tecentriq during labor and delivery has not been established.
Lactation: It is not known whether Tecentriq is excreted in human breast milk. No studies have been conducted to assess the impact of Tecentriq on milk production or its presence in breast milk. As the potential for harm to the nursing infant is unknown, a decision must be made to either discontinue breast-feeding or discontinue Tecentriq therapy.
Adverse Reactions
Clinical Trials: The corresponding frequency category for each adverse drug reaction is based on the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000).
Tecentriq monotherapy: The safety of Tecentriq monotherapy is based on pooled data on 3178 patients with multiple tumor types, with supporting data from the estimated cumulative exposure on >13000 patients across all clinical trials. Table 12 summarizes the adverse drug reactions (ADRs) that have been reported in association with the use of Tecentriq. (See Table 12.)

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Click on icon to see table/diagram/image

Tecentriq combination therapy: Additional ADRs identified in clinical trials (not reported in monotherapy trials) associated with the use of Tecentriq in combination therapy across multiple indications are summarized in Table 13. ADRs with a clinically relevant difference when compared to monotherapy (refer to Table 13) are also presented. (See Table 13.)

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Additional information for selected adverse reactions: The data as follows reflect information for significant adverse reactions for Tecentriq monotherapy. Details for the significant adverse reactions for Tecentriq when given in combination are presented if clinically relevant differences were noted in comparison to Tecentriq monotherapy. See General under Precautions for management of the following: Immune-related pneumonitis: Pneumonitis occurred in 2.7% (87/3178) of patients who received Tecentriq monotherapy. Of the 87 patients, one event was fatal. The median time to onset was 3.4 months (range: 0.1 to 24.8 months). The median duration was 1.4 months (range: 0 to 21.2+ months; + denotes a censored value). Pneumonitis led to discontinuation of Tecentriq in 12 (0.4%) patients. Pneumonitis requiring the use of corticosteroids occurred in 1.6% (51/3178) of patients receiving Tecentriq.
Immune-related hepatitis: Hepatitis occurred in 2.0 (62/3178) of patients who received Tecentriq monotherapy. Of the 62 patients, two events were fatal. The median time to onset was1.5 months; (range: 0.2 to 18.8 months). The median duration was 2.1 months (range: 0 to 22.2+ months; + denotes a censored). Hepatitis led to discontinuation of Tecentriq in 6 (0.2%) patients. Hepatitis requiring the use of corticosteroids occurred in 0.6% (18/3178) of patients receiving Tecentriq.
Immune-related colitis: Colitis occurred in 1.1% (34/3178) of patients who received Tecentriq. The median time to onset 4.7 months (range 0.5 to 17.2 months). The median duration was 1.2 months (range: 0.1 to 17.8+ months; + denotes a censored value). Colitis led to discontinuation of Tecentriq in 8 (0.3%) patients. Colitis requiring the use of corticosteroids occurred in 0.6% (19/3178) of patients receiving Tecentriq.
Immune-related endocrinopathies: Thyroid Disorders: Hypothyroidism occurred in 5.2% (164/3178) of patients who received Tecentriq monotherapy. The median time to onset was 4.9 months (range 0 to 31.3 months). Hypothyroidism occurred in 24.3% (134/552) of patients who received Tecentriq with bevacizumab.
Hyperthyroidism occurred in 0.9% (30/3178) of patients who received Tecentriq monotherapy. The median time to onset was 2.1 months (range 0.7 to 15.7 months). The median duration was 2.6 months (range: 0 + to 17.1+ months; + denotes a censored value). Hyperthyroidism occurred in 6.3% (35/552) of patients who received Tecentriq with bevacizumab.
Adrenal Insufficiency: Adrenal insufficiency occurred in 0.3% (11/3178) of patients who received Tecentriq monotherapy. The median time to onset was 5.5 months (range: 0.1 to 19.0 months). The median duration was 16.8 months (range: 0 to 16.8 months). Adrenal insufficiency led to discontinuation of Tecentriq in 1 (<0.1%) patient. Adrenal insufficiency requiring the use of corticosteroids occurred in 0.3% (9/3178) of patients receiving Tecentriq.
Hypophysitis: Hypophysitis occurred in <0.1% (2/3178) of patients who received Tecentriq monotherapy. The median time to onset was 7.2 months (range: 0.8 to 13.7 months). One patient required the use of corticosteroids and treatment with Tecentriq was discontinued.
Hypophysitis occurred in 0.8% (3/393) of patients who received Tecentriq with bevacizumab, paclitaxel, and carboplatin. The median time to onset was 7.7 months (range: 5.0 to 8.8 months). All three patients required the use of corticosteroids.
Hypophysitis occurred in 0.5% (3/552) of patients who received Tecentriq with bevacizumab. The median time to onset was 5.7 months (range: 0.7 to 9.1 months). Two of the three patients required the use of corticosteroids.
Diabetes Mellitus: Diabetes mellitus occurred in 0.3% (10/3178) of patients who received Tecentriq monotherapy. The median time to onset was 4.2 months (range 0.1 to 9.9 months). The median duration was 1.6 months (range: 0.1 to 15.2+ months; + denotes a censored value). Diabetes mellitus led to the discontinuation of Tecentriq in 3 (< 0.1%) patients.
Immune-related meningoencephalitis: Meningoencephalitis occurred in 0.4% (14/3178) of patients who received Tecentriq monotherapy. The median time to onset was 0.5 months (range 0 to 12.5 months). The median duration was 0.7 months (range 0.2 to 14.5 months; + denotes a censored valued). Meningoencephalitis requiring the use of corticosteroids occurred in 0.2% (6/3178) of patients receiving Tecentriq and all led to discontinuation of Tecentriq in 4 (0.1%) patients.
Immune-related neuropathies: Neuropathies, including Guillain-Barré syndrome and demyelinating polyneuropathy, occurred in 0.2% (5/3178) of patients who received Tecentriq monotherapy. The median time to onset was 7.0 months (range: 0.6 to 8.1 months). The median duration was 8.0 months (0.6 to 8.3+ months; +denotes a censored valued). Guillain-Barré syndrome led to the discontinuation of Tecentriq in 1 (<0.1%) patient. Guillain-Barré syndrome requiring the use of corticosteroids occurred in < 0.1% (2/3178) of patients receiving Tecentriq.
Immune-related pancreatitis: Pancreatitis, including increased amylase and lipase levels, occurred in 0.6% (18/3178) of patients who received Tecentriq monotherapy. The median time to onset was 5.0 months (range: 0.3 to 16.9 months). The median duration was 0.8 months (range 0.1 to 12.0+ months; +denotes a censored value) Pancreatitis led to discontinuation of Tecentriq in 3 (<0.1%) patients. Pancreatitis requiring the use of corticosteroids occurred in 0.1% ( 4/3174) of patients receiving Tecentriq.
Immune-related myositis: Myositis occurred in 0.4% (13/3178) of patients who received Tecentriq monotherapy. The median time to onset was 5.1 months (range: 0.7 to 11.0 months). The median duration was 5.0 months (range 0.7 to 22.6+ months, + denotes a censored value). Myositis led to discontinuation of Tecentriq in 1 (<0.1%) patient. Myositis requiring the use of corticosteroids occurred in 0.2% (7/3178) of patients receiving Tecentriq.
Immune-related nephritis: Nephritis, occurred in <0.1% (3/3178) of patients who received Tecentriq monotherapy. The median time to onset was 13.1 months (range: 9.0 to 17.5 months). The median duration was 2.8 days (range 0.5 to 9.5+ months; + denotes a censored value). Nephritis led to discontinuation of Tecentriq in 2 (<0.1%) patients. One patient required the use of corticosteroids.
Postmarketing Experience: No new adverse drug reactions have been identified from postmarketing experience.
Drug Interactions
No formal pharmacokinetic drug-drug interaction studies have been conducted with atezolizumab. Since atezolizumab is cleared from the circulation through catabolism, no metabolic drug-drug interactions are expected.
Caution For Usage
Special Instructions for Use, Handling and Disposal: Instruction for dilution: Tecentriq should be prepared by a healthcare professional using aseptic technique. Withdraw the required volume of Tecentriq liquid concentrate from the vial and dilute to the required administration volume with 0.9% sodium chloride solution. Dilute with 0.9% sodium chloride injection only. After dilution, the final concentration of the diluted solution should be between 3.2 and 16.8 mg/ mL.
This medicinal product must not be mixed with other medicinal products.
No preservative is used in Tecentriq, therefore, each vial is for single use only. Discard any unused portion.
Incompatibilities: No incompatibilities have been observed between Tecentriq and IV bags with product-contacting surfaces of polyvinyl chloride (PVC), polyolefin bags polyethylene (PE) or polypropylene (PP). In addition, no incompatibilities have been observed with in-line filter membranes composed of polyethersulfone or polysulfone, and infusion sets and other infusion aids composed of PVC, PE, polybutadiene, or polyetherurethane.
Disposal of unused/expired medicines: The release of pharmaceuticals in the environment should be minimized. Medicines should not be disposed of via wastewater and disposal through household waste should be avoided. Use established "collection systems," if available in the location.
Storage
Vials: Store at 2 °C to 8 °C.
Tecentriq should be protected from light.
Do not freeze. Do not shake.
Shelf-Life: As registered locally.
The diluted solution for infusion should be used immediately. If the solution is not used immediately, it can be stored for up to 24 hours at 2°C to 8°C, or 8 hours at ambient temperature (≤ 25°C).
ATC Classification
L01XC32 - atezolizumab ; Belongs to the class of monoclonal antibodies, other antineoplastic agents. Used in the treatment of cancer.
Presentation/Packing
Infusion conc (vial) 840 mg/14 mL x 1's. 1,200 mg/20 mL (colorless to slightly yellow solution) x 1's.
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