Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer
Phase 3
Active, not recruiting
- Conditions
- Small Cell Lung Carcinoma
- Interventions
- Registration Number
- NCT04665856
- Lead Sponsor
- Hoffmann-La Roche
- Brief Summary
The purpose of this multicenter study in China is to evaluate the safety and efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with untreated extensive-stage small cell lung cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 123
Inclusion Criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Histologically or cytologically confirmed Extensive-Stage Small Cell Lung Cancer (ES-SCLC) per the modified Veterans Administration Lung Study Group (VALG) staging system
- No prior systemic treatment for ES-SCLC
- For participants who have received prior chemoradiotherapy for limited-stage SCLC must have had treatment with curative intent and a treatment-free interval of at least 6 months between the last dose/cycle of chemotherapy, thoracic radiotherapy, or chemoradiotherapy and the diagnosis of ES-SCLC
- Measurable diseases as defined by RECIST v1.1
- Submission of a pre-treatment tumor tissue sample
- Adequate hematologic and end-organ function
- Participants not receiving therapeutic anticoagulation with International Normalized Ratio (INR) and Activated Clotting Time (aPTT) </= 1.5 x ULN
- Participants receiving therapeutic anticoagulation: stable anticoagulant regimen
- Negative Human Immunodeficiency Virus (HIV) test at screening
- Negative hepatitis B surface antigen (HBsAg) test at screening
- Positive hepatitis B surface antibody (HBsAb) test at screening, or negative HBsAb at screening accompanied by either of the following: negative total hepatitis B core antibody (HBcAb) and/or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test
- Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test
- Negative Epstein-Barr virus (EBV) viral capsid antigen (VCA) IgM test or negative EBV polymerase chain reaction (PCR) test at screening
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs
- For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm.
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Exclusion Criteria
- Symptomatic or actively progressing central nervous system (CNS) metastases
- Spinal cord compression
- Leptomeningeal disease
- Uncontrolled pleural effusion, pericardial effusion, or ascites
- Uncontrolled or symptomatic hypercalcemia
- Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease, or current alcohol abuse
- Malignancies other than SCLC within 5 years prior to randomization
- Active or history of autoimmune disease or immune deficiencies
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest Computer Tomography (CT) scan
- Known active tuberculosis, Current treatment with anti-viral therapy for HBV or HCV
- Severe chronic or active infection
- Treatment with therapeutic oral or IV antibiotics
- Significant cardiovascular disease
- Major surgical procedure other than for diagnosis
- Prior allogeneic bone marrow transplantation or solid organ transplant
- Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition
- Administration of a live, attenuated vaccine
- Prior treatment with CD137 agonists, T-cell co-stimulating, or immune checkpoint blockade therapies
- Treatment with systemic immunostimulatory agents
- Treatment with systemic immunosuppressive medications
- History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to Chinese Hamster Ovary (CHO) cell products or to any component of the tiragolumab or atezolizumab formulations
- History of allergic reactions to carboplatin or etoposide
- Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the final dose of atezolizumab or within 90 days after the final dose of tiragolumab or for 6 months after the final dose of carboplatin or etoposide.
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Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + Atezolizumab + Carboplatin and Etoposide Tiragolumab Matching Placebo Induction treatment with placebo plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo plus atezolizumab for 21-day cycles Tiragolumab + Atezolizumab + Carboplatin and Etoposide Tiragolumab Induction treatment with tiragolumab plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab plus atezolizumab for 21-day cycles. Placebo + Atezolizumab + Carboplatin and Etoposide Atezolizumab Induction treatment with placebo plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo plus atezolizumab for 21-day cycles Tiragolumab + Atezolizumab + Carboplatin and Etoposide Atezolizumab Induction treatment with tiragolumab plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab plus atezolizumab for 21-day cycles. Tiragolumab + Atezolizumab + Carboplatin and Etoposide Carboplatin Induction treatment with tiragolumab plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab plus atezolizumab for 21-day cycles. Tiragolumab + Atezolizumab + Carboplatin and Etoposide Etoposide Induction treatment with tiragolumab plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with tiragolumab plus atezolizumab for 21-day cycles. Placebo + Atezolizumab + Carboplatin and Etoposide Carboplatin Induction treatment with placebo plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo plus atezolizumab for 21-day cycles Placebo + Atezolizumab + Carboplatin and Etoposide Etoposide Induction treatment with placebo plus atezolizumab and CE will be administered on a 21-day cycle for 4 cycles. Following the induction phase, participants will continue maintenance therapy with placebo plus atezolizumab for 21-day cycles
- Primary Outcome Measures
Name Time Method Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set (PAS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 49 months) Overall Survival (OS) in the PAS From randomization to death from any cause (up to approximately 49 months)
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab Predose on Day 1 of Cycles (each cycle=21 days) 1, 2, 3, 4, 8, 12, 16 and at TD visit (up to approximately 49 months) PFS in the Full Analysis Set (FAS) From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 49 months) OS in the FAS From randomization to death from any cause (up to approximately 49 months) Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS From randomization up to approximately 49 months Investigator-Assessed Confirmed ORR in the FAS From randomization up to approximately 49 months Investigator-Assessed Duration of Response (DOR) in the PAS From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 49 months) Investigator-Assessed DOR in the FAS From the first occurrence of a documented confirmed objective response to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 49 months) Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS Month 6, Month 12 Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS Month 6, Month 12 Overall Survival Rates at 12 Months and 24 Months in the PAS Month 12, Month 24 Overall Survival Rates at 12 Months and 24 Months in the FAS Month 12, Month 24 Time to Confirmed Deterioration (TTCD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score in the PAS Up to approximately 49 months TTCD Assessed Using EORTC QLQ-C30 Score in the FAS Up to approximately 49 months Percentage of Participants with Adverse Events, Determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0) Up to approximately 49 months Serum Concentration of Tiragolumab at Specified Timepoints Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at treatment discontinuation (TD) visit (up to approximately 49 months) Serum Concentration of Atezolizumab at Specified Timepoints Cycle 1 (each cycle=21 days), Day 1: predose, 0.5 hour (h) postdose; Cycles 2, 3, 4, 8, 12, 16, Day 1: predose and at TD visit (up to approximately 49 months)
Trial Locations
- Locations (16)
Beijing Chest Hospital
🇨🇳Beijing, China
Zhejiang Cancer Hospital
🇨🇳Hangzhou, China
Beijing Cancer Hospital
🇨🇳Beijing, China
the First Affiliated Hospital of Bengbu Medical College
🇨🇳Bengbu City, China
the First Hospital of Jilin University
🇨🇳Changchun, China
Fujian Provincial Cancer Hospital
🇨🇳Fuzhou City, China
Cancer Center of Guangzhou Medical University
🇨🇳Guangzhou, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, China
The 1st Affiliated Hospital of Nanchang Unversity
🇨🇳Nanchang, China
Shanghai Chest Hospital
🇨🇳Shanghai, China
Zhongshan Hospital Fudan University
🇨🇳Shanghai, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, China
Cancer Hospital of Shantou University Medical College
🇨🇳Shantou, China
Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan City, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China