A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients With Untreated Extensive-Stage Small Cell Lung Cancer
Trial Snapshot
- Phase
- Phase 3
- Status
- Active, not recruiting
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 123
- Locations
- 29
- Primary Endpoint
- Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set (PAS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
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.
Arms & Interventions
Tiragolumab + Atezolizumab + Carboplatin and 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.
Intervention: Tiragolumab (Drug)
Tiragolumab + Atezolizumab + Carboplatin and 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.
Intervention: Atezolizumab (Drug)
Tiragolumab + Atezolizumab + Carboplatin and 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.
Intervention: Carboplatin (Drug)
Tiragolumab + Atezolizumab + Carboplatin and 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.
Intervention: Etoposide (Drug)
Placebo + Atezolizumab + Carboplatin and 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
Intervention: Atezolizumab (Drug)
Placebo + Atezolizumab + Carboplatin and 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
Intervention: Carboplatin (Drug)
Placebo + Atezolizumab + Carboplatin and 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
Intervention: Etoposide (Drug)
Placebo + Atezolizumab + Carboplatin and 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
Intervention: Tiragolumab Matching Placebo (Drug)
Outcomes
Primary Outcomes
Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set (PAS)
Time Frame: Up to 32.3 months
PFS was defined as time from randomization to the first occurrence of disease progression (PD), as assessed by the investigator using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm).
Overall Survival (OS) in the PAS
Time Frame: Up to 32.3 months
OS was defined as the time from the date of randomization to the date of death from any cause.
Secondary Outcomes
- Investigator-Assessed DOR in the FAS(Up to 32.3 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 Rate 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 66 months)
- Percentage of Participants With Adverse Events(Up to 66 months)
- TTCD Assessed Using EORTC QLQ-C30 Score in the FAS(Up to approximately 66 months)
- Maximum Plasma Concentration (Cmax) of Tiragolumab(Cycle 1 Day 1, 30 mins post end of infusion (EOI) (cycle length= 21 days))
- Minimum Plasma Concentration (Cmin) of Tiragolumab(Pre-dose, Day 1 of Cycles 2, 3, 4, 8, 12, 16 (cycle length= 21 days))
- Cmax of Atezolizumab(Cycle 1 Day 1, 30 mins post EOI (cycle length= 21 days))
- Cmin of Atezolizumab(Pre-dose, Day 1 of Cycles 2, 3, 4, 8, 12, 16 (cycle length= 21 days))
- 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))
- Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS(Up to 32.3 months)
- PFS in the FAS(Up to 32.3 months)
- OS in the FAS(Up to 32.3 months)
- Investigator-Assessed Confirmed ORR in the FAS(Up to 32.3 months)
- Investigator-Assessed Duration of Response (DOR) in the PAS(Up to 32.3 months)