Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer

Small Cell Lung Carcinoma Clinical Trial

— SKYSCRAPER-02C  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04665856
• Other study ID #: YO42373
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 22, 2020
• Est. completion date: April 15, 2025

Study information

• Verified date: April 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 123
• Est. completion date: April 15, 2025
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Small Cell Lung Carcinoma

Intervention

Drug:
• Tiragolumab
Tiragolumab at a fixed dose of 600 milligrams (mg), administered by intravenous (IV) infusion, every 3 weeks (Q3W) on Day 1 of each 21-day cycle.
• Atezolizumab
Atezolizumab at a fixed dose of 1200 mg, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.
• Carboplatin
Carboplatin administered IV to achieve an initial target area under the concentration time curve (AUC) of 5 mg/mL/min, Q3W on Day 1 of each 21-day cycle for 4 cycles.
• Etoposide
Etoposide 100 mg/m^2, administered by IV infusion, Q3W on Day 1, 2 and 3 of each 21-day cycle for 4 cycles.
• Tiragolumab Matching Placebo
Matching placebo, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing
China	Beijing Chest Hospital; Oncology Department	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 City
China	Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department	Hangzhou City
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 City
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

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Overall Survival (OS) in the PAS		From randomization to death from any cause (up to approximately 49 months)
Secondary	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)
Secondary	OS in the FAS		From randomization to death from any cause (up to approximately 49 months)
Secondary	Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS		From randomization up to approximately 49 months
Secondary	Investigator-Assessed Confirmed ORR in the FAS		From randomization up to approximately 49 months
Secondary	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)
Secondary	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)
Secondary	Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS		Month 6, Month 12
Secondary	Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS		Month 6, Month 12
Secondary	Overall Survival Rates at 12 Months and 24 Months in the PAS		Month 12, Month 24
Secondary	Overall Survival Rates at 12 Months and 24 Months in the FAS		Month 12, Month 24
Secondary	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
Secondary	TTCD Assessed Using EORTC QLQ-C30 Score in the FAS		Up to approximately 49 months
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)