Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Participants With Untreated Extensive-Stage Small Cell Lung Cancer (SKYSCRAPER-02C)

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

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 Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Carcinoma
• Intervention / Treatment: Drug: Tiragolumab; Drug: Atezolizumab; Drug: Carboplatin; Drug: Etoposide; Drug: Tiragolumab Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 123
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 101149
    • Beijing Chest Hospital; Oncology Department
  • Bengbu City, China, 233000
    • The First Affiliated Hospital of Bengbu Medical College
  • Changchun, China, 130021
    • The First Hospital of Jilin University
  • Fuzhou City, China, 350014
    • Fujian Provincial Cancer Hospital
  • Guangzhou, China, 510000
    • Cancer Center of Guangzhou Medical University
  • Hangzhou City, China, 310022
    • Zhejiang Cancer Hospital; Zhejiang Cancer Hospital cancer department
  • Hangzhou City, China, 310016
    • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Nanchang, China, 330019
    • The 1st Affiliated Hospital of Nanchang Unversity
  • Shanghai, China, 200000
    • Shanghai Chest Hospital
  • Shanghai, China, 200032
    • Zhongshan Hospital Fudan University
  • Shanghai City, China, 200120
    • Fudan University Shanghai Cancer Center
  • Shantou, China, 515041
    • Cancer Hospital of Shantou University Medical College
  • Wuhan City, China, 430022
    • Wuhan Union Hospital Tongji Medical College, Huazhong University of Science and Technology
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	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.; Other Names: MTIG7192A; Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq; Drug: 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.; Drug: 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.
Placebo Comparator: 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	Drug: Atezolizumab; Atezolizumab at a fixed dose of 1200 mg, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.; Other Names: Tecentriq; Drug: 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.; Drug: 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.; Drug: Tiragolumab Matching Placebo; Matching placebo, administered by IV infusion, Q3W on Day 1 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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)
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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2020
• Primary Completion (Actual): August 31, 2023
• Study Completion (Estimated): April 15, 2025

Study Registration Dates

• First Submitted: December 7, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Carboplatin; Etoposide; Atezolizumab
• Other Study ID Numbers: YO42373

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes