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The sponsor's decision was based on the negative results of SKYSCRAPER-02.
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This is a multicenter, double-blind, placebo-controlled, randomized, phase II study to investigate the efficacy and safety of Atezolizumab with or without Tiragolumab as consolidation therapy in participants with limited stage small cell lung cancer who have not progressed during/after chemoradiotherapy.
Participants can receive concurrent or sequential chemoradiotherapy (CRT) as per local standard of care, but they must be randomized within 6 weeks from completion of chemoradiotherapy. Participants should receive 4 cycles of chemotherapy and radiotherapy dose of 56-64 Gy (once daily) before randomization, and those participants who have not progressed during/after CRT will be stratified by response to CRT, radiotherapy timing, and be randomized in a 1:1 ratio to Atezolizumab+Tiragolumab arm or Atezolizumab+placebo arm.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm A: Atezolizumab + Tiragolumab | Experimental | Participants will receive atezolizumab + tiragolumab intravenously on the first day of each cycle. One cycle of therapy will be defined as 21 days. Atezolizumab and tiragolumab treatment will continue up to 17 doses unless investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or patient decision to withdraw from therapy, or death (whichever occurs first). |
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| Arm B: Atezolizumab + Placebo | Experimental | Participants will receive atezolizumab + placebo on the first day of each cycle. One cycle of therapy will be defined as 21 days. Atezolizumab and placebo treatment will continue up to 17 doses unless investigator-assessed loss of clinical benefit, unacceptable toxicity, investigator or patient decision to withdraw from therapy, or death (whichever occurs first). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atezolizumab | Drug | Atezolizumab will be administered at a dose of 1200 mg intravenously on the first day of each 21-day cycle. |
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| Measure | Description | Time Frame |
|---|---|---|
| Investigator Assessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population | PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1. | Randomization up to approximately 48 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Survival (OS) in the ITT Population | OS is defined as the time from randomization to death from any cause or last follow-up. | Randomization up to approximately 48 months |
| PFS Rate at 1 Year and 2 Years in the ITT Ppulation |
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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 |
|---|---|---|---|---|---|---|
| Beijing Cancer Hospital | Beijing | 100142 | China | |||
| Jilin 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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| Tiragolumab | Drug | Tiragolumab will be administered at a dose of 600 mg intravenously on the first day of each 21-day cycle. |
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| Placebo | Other | Placebo matching to tiragolumab will be administered at a dose of 600 mg intravenously on the first day of each cycle. |
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PFS rate at 1 year and 2 years, defined as the proportion of patients remaining stable disease or ongoing response per RECIST v1.1 at 1 year and 2 years from the time of randomization.
| Baseline to 1 Year and 2 Years |
| OS Rate at 1 Year, 2 Years and 3 Years in the ITT Population | OS rate at 1 year, 2 years and 3 years is defined as the proportion of patients remaining alive 1 year, 2 years and 3 years from the time of randomization. | Baseline to 1 Year, 2 Years and 3 Years |
| Objective Response Rate (ORR) in the ITT Population | ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1 in patients who have measurable disease at baseline. | Randomization up to approximately 48 months |
| Duration of Response (DOR) in the ITT Population | DOR is defined as the time interval from first occurrence of a documented objective response to the time of disease progression as determined by the investigator according to the RECIST v1.1 or death from any cause, whichever occurs first, in the patients who have experienced a CR or PR (unconfirmed) during the study. | Time from first documentation of complete response (CR) or partial response (PR) up to approximately 48 months |
| Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Response to Chemoradiotherapy (CRT) [Stable Disease (SD) vs. Complete Response (CR)/Partial Response (PR)] | PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1. | Randomization up to approximately 33 months |
| Overall Survival (OS) in the ITT Population by Response to CRT (SD vs. CR/PR) | OS is defined as the time from randomization to death from any cause or last follow-up. | Randomization up to approximately 48 months |
| Objective Response Rate (ORR) in the ITT Population by Response to CRT (SD vs. CR/PR) | ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1. | Randomization up to approximately 48 months |
| Investigator Accessed Progression-Free Survival (PFS) in the Intent-To-Treat (ITT) Population by Radiotherapy Timing (Concurrent vs. Sequential) | PFS is defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be calculated based on disease status evaluated by the investigator according to RECIST v1.1. | Randomization up to approximately 48 months |
| Overall Survival (OS) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential) | OS is defined as the time from randomization to death from any cause or last follow-up. | Randomization up to approximately 48 months |
| Objective Response Rate (ORR) in the ITT Population by Radiotherapy Timing (Concurrent vs. Sequential) | ORR is defined as the percentage of patients who attain complete response (CR) or partial response (PR) according to RECIST v1.1. | Randomization up to approximately 48 months |
| Percentage of Participants With All Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population | Baseline up to approximately 48 months |
| Percentage of Participants With Serious and Non-Serious Immune Mediated Adverse Events Related to Atezolizumab and Atezolizumab + Tiragolumab Treatment in the ITT Population | Baseline up to approximately 48 months |
| Percentage of Participants With All Adverse Events Related to Treatment in the ITT Population | Baseline up to approximately 48 months |
| Time to Deterioration (TTD) in Patient-Rported Lung Cancer Symptoms | TTD is defined as the time from randomization to a patient's first ≥10-point score change from baseline in a scale maintained for at least two consecutive PRO assessments, or followed by death within 3 weeks of the first ≥10-point score change. | Randomization up to approximately 48 months |
| EORTC QLQ-C30 Score | EORTC QLQ-C30, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire-Core 30 Questionnaire, is a validated, reliable self-report measure. It consists of 30 questions that assess five aspects of patient functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), global health/quality of life, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties) with a recall period of the previous week. Scale scores can be obtained for the multi-item scales. | Day 1 of first 3 cycles (each cycle is 21 days) then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months |
| EORTC QLQ-LC13 Score | The EORTC, European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire, QLQ-LC13 is a modular supplement to the EORTC quality-of-life questionnaire for use in lung cancer. This module incorporates one multiple-item scale to assess dyspnea and a series of single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. | Day 1 of first 3 cycles (cycle length=21 days), then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months |
| EuroQol 5-Dimension 5-Level (EQ-5D-5L) Index Based and Visual Analogue Scale (VAS) Scores | The EuroQol 5-Dimension Questionnaire, 5-level version (EQ-5D-5L), is a validated self-report health status questionnaire that is used to calculate a health status utility score for use in health economic analyses. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analogue scale (VAS) that measures health state. Published weighting systems allow for creation of a single composite score of the patient's health status. | Day 1 of first 3 cycles (each cycle is 21 days) then with tumor assessments & 3 months after radiographic disease progression or for patients who continue atezolizumab after radiographic disease progression loss of clinical benefit up to approx 48 months |
| Changchun |
| 132013 |
| China |
| Hu Nan Provincial Cancer Hospital | Changsha | 410006 | China |
| Sichuan Cancer Hospital | Chengdu | 610041 | China |
| Southwest Hospital , Third Military Medical University | Chongqing | 400038 | China |
| Fujian Cancer Hospital | Fuzhou | 350014 | China |
| The First Affiliated Hospital of Guangzhou Medical University | Guangzhou | 510120 | China |
| Sun Yet-sen University Cancer Center | Guangzhou | 510663 | China |
| Harbin Medical University Cancer Hospital | Harbin | 150081 | China |
| Anhui Province Cancer Hospital | Hefei | 230031 | China |
| Shandong Cancer Hospital | Jinan | 250117 | China |
| Guangxi Cancer Hospital of Guangxi Medical University | Nanning | 530021 | China |
| Fudan University Shanghai Cancer Center; Medical Oncology | Shanghai | 201315 | China |
| Tianjin Cancer Hospital | Tianjin | 300060 | China |
| Tumor Center,Union Hospital, Tongji Medical College, Huazhong University of Science and Technology | Wuhan | 430023 | China |
| First Affiliated Hospital of Medical College of Xi'an Jiaotong University | Xi'an | 710061 | China |
| Henan Cancer Hospital | Zhengzhou | 450008 | China |
| ID | Term |
|---|---|
| D055752 | Small Cell Lung Carcinoma |
| 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 |
| C000730814 | Tiragolumab |
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