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

• ClinicalTrials.gov Identifier: NCT04256421
• Recruitment Status: Active, not recruiting
• First Posted: February 5, 2020
• Last Update Posted: May 26, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: January 31, 2020
• First Posted Date: February 5, 2020
• Last Update Posted Date: May 26, 2023
• Actual Study Start Date: February 4, 2020
• Actual Primary Completion Date: September 6, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 13, 2021)

• Investigator-Assessed Progression Free Survival (PFS) in the Primary Analysis Set (PAS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months) ]
• Overall Survival (OS) in the PAS [ Time Frame: From randomization to death from any cause (up to 50 months) ]

Original Primary Outcome Measures (submitted: February 3, 2020)

• Progression Free Survival (PFS) [ Time Frame: From randomization to disease progression or death (whichever occurs first), up to 43 months ]
• Overall Survival (OS) [ Time Frame: From randomization to death from any cause, up to 43 months ]

Current Secondary Outcome Measures (submitted: December 13, 2021)

• PFS in the Full Analysis Set (FAS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 50 months) ]
• OS in the FAS [ Time Frame: From randomization to death from any cause (up to 50 months) ]
• Investigator-Assessed Confirmed Objective Response Rate (ORR) in the PAS [ Time Frame: From randomization up to 50 months ]
• Investigator-Assessed Confirmed ORR in the FAS [ Time Frame: From randomization up to 50 months ]
• Investigator-Assessed Duration of Response (DOR) in the PAS [ Time Frame: From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first ( up to 50 months) ]
• Investigator-Assessed DOR in the FAS [ Time Frame: From the first occurrence of a documented confirmed objective response to disease progression or death from any cause, whichever occurs first ( up to 50 months) ]
• Investigator-Assessed PFS Rates at 6 Months and 12 Months in the PAS [ Time Frame: 6 months, 12 months ]
• Investigator-Assessed PFS Rates at 6 Months and 12 Months in the FAS [ Time Frame: 6 months, 12 months ]
• Overall Survival Rates at 12 Months and 24 Months in the PAS [ Time Frame: 12 months, 24 months ]
• Overall Survival Rates at 12 Months and 24 Months in the FAS [ Time Frame: 12 months, 24 months ]
• 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 [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration up to 50 months ]
  TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
• TTCD Assessed Using EORTC QLQ-C30 Score in the FAS [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration up to 50 months ]
  TTCD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS)/quality of life (QoL) and functioning from baseline that must be held for at least two consecutive assessments or an initial clinically meaningful decrease above baseline followed by death. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
• Percentage of Participants With Adverse Events [ Time Frame: Up to 50 months ]
• Minimum Serum Concentration (Cmin) of Tiragolumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 50 months). ]
• Cmin of Atezolizumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) ]
• Maximum Serum Concentration (Cmax) of Tiragolumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) ]
• Cmax of Atezolizumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) ]
• Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab [ Time Frame: Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) ]
• Percentage of Participants With ADAs to Atezolizumab [ Time Frame: Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 50 months) ]
• Change from Baseline in EuroQol 5-Dimension, 5-Level (EQ-5D-5L) Index-based and Visual Analog Scale Scores [ Time Frame: From baseline up to 50 months ]
  The EQ-5D-5L is a validated self-report health status questionnaire that is used to calculate a health status utility score for use in health economic analyses. There are two components to the EQ-5D-5L: a five-item health state profile that assesses mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, as well as a visual analog scale (VAS) that measures health state. A single composite score is calculated based on the responses as an indicator of the participant's health status.

Original Secondary Outcome Measures (submitted: February 3, 2020)

• Confirmed Objective Response Rate (ORR) [ Time Frame: From randomization up to disease progression or relapse or death, whichever occurs first, up to 43 months ]
• Duration of Response (DOR) [ Time Frame: From randomization up to disease progression or relapse or death, whichever occurs first, up to 43 months ]
• PFS Rates at 6 Months and 12 Months [ Time Frame: 6 months, 12 months ]
• Overall Survival Rates at 12 Months and 24 Months [ Time Frame: 12 months, 24 months ]
• Time to Sustained Deterioration (TTSD) Assessed Using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core (QLQ-C30) Score [ Time Frame: Up to 43 months ]
  TTSD using EORTC QLQ-C30 is an initial 10-point decrease in global health status (GHS) and physical functioning from baseline that must be held for all subsequent assessment timepoints or followed by death attributable to cancer progression. EORTC QLQ-C30: a self-reported measure, consisting of 30 questions that assess 5 aspects of participants functioning (physical, emotional, role, cognitive and social), 3 symptom scales (fatigue, nausea and vomiting and pain), GHS and quality of life (QoL), and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties) with a recall period of the previous week. Functioning items are scored on a 4-point scale: 1=Not at all to 4=Very much, with higher score indicating worse outcome. Symptom items (GHS and QoL) are scored on a 7-point scale: 1=Very poor to 7=Excellent. Scores will be linearly transformed with a minimum score of 0 and maximum score of 100. Higher score indicates better outcome.
• Percentage of Participants With Adverse Events [ Time Frame: Up to 43 months ]
• Minimum Serum Concentration (Cmin) of Tiragolumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 43 months). ]
• Cmin of Atezolizumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 43 months) ]
• Maximum Serum Concentration (Cmax) of Tiragolumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 43 months) ]
• Cmax of Atezolizumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (each cycle is 21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 43 months) ]
• Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab [ Time Frame: Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 43 months) ]
• Percentage of Participants With ADAs to Atezolizumab [ Time Frame: Predose on Day 1 of Cycles 1 (each cycle is 21 days), 2, 3, 4, 8,12 and 16 and at TD visit (up to 43 months) ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Atezolizumab Plus Carboplatin and Etoposide With or Without Tiragolumab in Patients 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 (Anti-Tigit Antibody) in Patients With Untreated Extensive-Stage Small Cell Lung Cancer

Brief Summary

This study will evaluate the efficacy of tiragolumab plus atezolizumab and carboplatin and etoposide (CE) compared with placebo plus atezolizumab and CE in participants with chemotherapy-naive extensive-stage small cell lung cancer (ES-SCLC). Eligible participants will be stratified by Eastern Cooperative Oncology Group (ECOG) Performance Status (0 vs. 1), LDH (</= upper limit of normal [ULN] vs. > ULN), and presence or history of brain metastasis (yes vs. no) and randomly assigned in a 1:1 ratio to receive one of the following treatment regimens during induction phase:

• Arm A: Tiragolumab plus atezolizumab plus CE
• Arm B: Placebo plus atezolizumab plus CE

Following the induction phase, participants will continue maintenance therapy with either atezolizumab plus tiragolumab (Arm A) or atezolizumab plus placebo (Arm B).

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Small Cell Lung Cancer

Intervention

• Drug: Tiragolumab
  Tiragolumab 600 milligrams (mg) administered by IV infusion on Day 1 of each 21-day cycle.
  Other Name: MTIG7192A
• Drug: Atezolizumab
  Atezolizumab 1200 mg administered by IV infusion on Day 1 of each 21-day cycle.
  Other Name: Tecentriq
• Drug: Carboplatin
  Carboplatin was administered by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
• Drug: Etoposide
  Etoposide 100 mg/m^2 administered by IV infusion on Days 1, 2 and 3 of each 21-day cycle for 4 cycles.
• Drug: Placebo
  Placebo administered by IV infusion on Day 1 of each 21-day cycle.

Study Arms

• Experimental: Tiragolumab + Atezolizumab + CE
  Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by tiragolumab on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
  Interventions:

  • Drug: Tiragolumab
  • Drug: Atezolizumab
  • Drug: Carboplatin
  • Drug: Etoposide
• Active Comparator: Placebo + Atezolizumab + CE
  Participants will receive atezolizumab on Day 1 of each 21-day cycle followed by placebo on Day 1 of each 21-day cycle. Carboplatin will be administered followed by etoposide on Day 1 for 4 cycles. Participants will also receive etoposide on Days 2 and 3.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Carboplatin
  • Drug: Etoposide
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: July 7, 2021): 490
• Original Estimated Enrollment (submitted: February 3, 2020): 400
• Estimated Study Completion Date: March 21, 2024
• Actual Primary Completion Date: September 6, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC)
• No prior systemic treatment for ES-SCLC
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Measurable disease, as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
• Adequate hematologic and end-organ function
• Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC

Exclusion Criteria:

• Symptomatic or actively progressing central nervous system (CNS) metastases
• Malignancies other than small cell lung cancer (SCLC) within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Positive test result for human immunodeficiency virus (HIV)
• Active hepatitis B or hepatitis C
• Severe infection at the time of randomization
• Treatment with any other investigational agent within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-cytotoxic T lymphocyte-associated protein 4 (anti-CTLA-4), anti-TIGIT, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug elimination half-lives prior to randomization

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Austria, Belgium, Brazil, Czechia, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Russian Federation, Serbia, Singapore, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: France

Administrative Information

• NCT Number: NCT04256421
• Other Study ID Numbers: GO41767; 2019-003301-97 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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/members/ourmembers/). 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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2023