Clinical trial NCT04665856: Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Small Cell Lung Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-12-14
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set (PAS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 49 months)
measure: Overall Survival (OS) in the PAS
timeFrame: From randomization to death from any cause (up to approximately 49 months)
Secondary outcomes:
measure: PFS in the Full Analysis Set (FAS)
timeFrame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 49 months)
measure: OS in the FAS
timeFrame: From randomization to death from any cause (up to approximately 49 months)
measure: Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS
timeFrame: From randomization up to approximately 49 months
measure: Investigator-Assessed Confirmed ORR in the FAS
timeFrame: From randomization up to approximately 49 months
measure: Investigator-Assessed Duration of Response (DOR) in the PAS
timeFrame: 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)
measure: Investigator-Assessed DOR in the FAS
timeFrame: 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)
measure: Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS
timeFrame: Month 6, Month 12
measure: Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS
timeFrame: Month 6, Month 12
measure: Overall Survival Rates at 12 Months and 24 Months in the PAS
timeFrame: Month 12, Month 24
measure: Overall Survival Rates at 12 Months and 24 Months in the FAS
timeFrame: Month 12, Month 24
measure: 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
timeFrame: Up to approximately 49 months
measure: TTCD Assessed Using EORTC QLQ-C30 Score in the FAS
timeFrame: Up to approximately 49 months
measure: Percentage of Participants with Adverse Events, Determined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)
timeFrame: Up to approximately 49 months
measure: Serum Concentration of Tiragolumab at Specified Timepoints
timeFrame: 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)
measure: Serum Concentration of Atezolizumab at Specified Timepoints
timeFrame: 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)
measure: Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab
timeFrame: 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)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Chest Hospital
city: Bengbu City
country: China
facility: the First Affiliated Hospital of Bengbu Medical College
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Fuzhou City
country: China
facility: Fujian Provincial Cancer Hospital
city: Guangzhou
country: China
facility: Cancer Center of Guangzhou Medical University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
city: Nanchang
country: China
facility: The 1st Affiliated Hospital of Nanchang Unversity
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
city: Shantou
country: China
facility: Cancer Hospital of Shantou University Medical College
city: Wuhan City
country: China
facility: Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: