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This study will evaluate the efficacy and safety of atezolizumab when given in combination with bevacizumab, investigator's choice of either paclitaxel or pemetrexed, and carboplatin compared with placebo given in combination with bevacizumab, paclitaxel or pemetrexed, and carboplatin in patients with chemotherapy-naive, Stage IV non-squamous Non-Small Cell Lung Cancer (NSCLC). The study will be conducted in two phases: Induction Phase and Maintenance Phase.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment A | Experimental | Participants will receive atezolizumab, bevacizumab, paclitaxel or pemetrexed, and carboplatin (in this order) by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with atezolizumab, bevacizumab and pemetrexed (if given in the induction phase) until unacceptable toxicity or loss of clinical benefit. |
|
| Treatment B | Placebo Comparator | Participants will receive placebo, bevacizumab, paclitaxel or pemetrexed, and carboplatin (in this order) by intravenous (IV) injection on Day 1 of each 21-day cycle for 4 cycles in the induction treatment. In the maintenance phase, participants will be treated with placebo, bevacizumab and pemetrexed (if given in the induction phase) until unacceptable toxicity or loss of clinical benefit. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Atezolizumab will be administered by IV infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression Free Survival (PFS) in the intent to treat (ITT) population, as determined by the investigator | PFS after randomization, defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 | Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) in the ITT population | OS after randomization, defined as the time from randomization to death from any cause. | Randomization to death from any cause (up to approximately 33 months) |
| PFS in the ITT population, as determined by IRF |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Hoffmann-La Roche | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Peking Union Medical College Hospital | Beijing | 100032 | China | |||
| Beijing Cancer Hospital |
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.clinicalstudydatarequest.com). Further details on Roche's criteria for eligible studies are available here (https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Roche.aspx). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research\_and\_development/who\_we\_are\_how\_we\_work/clinical\_trials/our\_commitment\_to\_data\_sharing.htm).
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|
| Placebo | Drug | Placebo matching to atezolizumab will be administered by IV infusion at a fixed dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle until unacceptable toxicity or loss of clinical benefit. |
|
| Bevacizumab | Drug | Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle. |
|
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| Paclitaxel | Drug | Paclitaxel will be administered by IV infusion at a dose of 175 mg/m2. |
|
| Pemetrexed | Drug | Pemetrexed will be administered by IV infusion at a dose of 500 mg/m2. |
|
| Carboplatin | Drug | Carboplatin will be administered by IV infusion to achieve an initial target AUC of 6 mg/mL/min. |
|
PFS after randomizationdefined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the an Independent Review Facility (IRF) according to RECIST v1.1 |
| Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| PFS in subgroup of participants with PD-L1 Expression, as determined by the investigator | PFS after randomization as determined by the investigator according to RECIST v1.1 in the subgroup of patients with PD-L1 expression defined by the SP263 immunohistochemistry (IHC) assay. | Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| PFS in the subgroup of participants with genomic alterations in EGFR or ALK gene, as determined by the investigator | PFS after randomization as determined by the investigator according to RECIST v1.1 in the subgroup of patients with genomic alterations in EGFR (i.e., sensitizing EGFR mutations) or ALK gene. | Randomization until the first occurence of disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| Objective Response Rate (ORR) in the ITT population | ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1. | Randomization until disease progression or death, which ever occurs first (up to approximately 33 months) |
| Duration of response (DOR) in the ITT population | DOR defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. | Randomization until the first occurence of a documented objective response to disease progression or death from any cause, whichever occures first (up to approximately 33 months) |
| Time to Confirmed Deterioration (TTCD) in physical functioning in the ITT population | (TTCD) in physical functioning, defined as the time from randomization to the first observed >=10-point decrease in the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) for cancer linearly transformed physical functioning scale score that is sustained for two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death within three weeks. | Randomization up until approximately 33 months |
| Percentage of Participants With Adverse Events | Randomization up to approximately 33 months |
| Beijing |
| 100142 |
| China |
| Beijing Chest Hospital; Oncology Department | Beijing | 101149 | China |
| the First Hospital of Jilin University | Changchun | 130021 | China |
| Jilin Cancer Hospital | Changchun | 132013 | China |
| West China Hospital, Sichuan University | Chengdu | 610041 | China |
| The 900th Hospital of PLA joint service support force | Fuzhou | 110016 | China |
| The First Affiliated Hospital of Guangzhou Medical University | Guangzhou | 510120 | China |
| Sir Run Run Shaw Hospital | Hangzhou | 310018 | China |
| Harbin Medical University Cancer Hospital | Harbin | 150081 | China |
| Shandong Cancer Hospital | Jinan | 250117 | China |
| Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School | Nanjing | 210008 | China |
| Guangxi Cancer Hospital of Guangxi Medical University | Nanning | 530021 | China |
| Nan Tong Tumor Hospital | Nantong | 226361 | China |
| Fudan University Shanghai Cancer Center | Shanghai | 200120 | China |
| Shanghai Pulmonary Hospital | Shanghai | 200433 | China |
| Liaoning cancer Hospital & Institute | Shenyang | 110042 | China |
| Union Hospital of Tongji Medical College, Dept. of Cancer Center; Cancer Center | Wuhan | 430023 | China |
| Hubei Cancer Hospital | Wuhan | 430079 | China |
| First Affiliated Hospital of Medical College of Xi'an Jiaotong University | Xi'an | 710061 | China |
| The First Affiliated Hospital of Xiamen University | Xiamen | 361003 | China |
| Zhejiang Cancer Hospital | Zhejiang | 310022 | China |
| Henan Cancer Hospital | Zhengzhou | 450008 | China |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| C000594389 | atezolizumab |
| D000068258 | Bevacizumab |
| D017239 | Paclitaxel |
| D000068437 | Pemetrexed |
| D016190 | Carboplatin |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D043823 | Taxoids |
| D043822 | Cyclodecanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D004224 | Diterpenes |
| D013729 | Terpenes |
| D006147 | Guanine |
| D007042 | Hypoxanthines |
| D011688 | Purinones |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D005971 | Glutamates |
| D024342 | Amino Acids, Acidic |
| D000596 | Amino Acids |
| D000600 | Amino Acids, Dicarboxylic |
| D056831 | Coordination Complexes |
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