A Study of Tiragolumab in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer (SKYSCRAPER-01)

• ClinicalTrials.gov Identifier: NCT04294810
• Recruitment Status: Recruiting
• First Posted: March 4, 2020
• Last Update Posted: May 25, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 2, 2020
• First Posted Date: March 4, 2020
• Last Update Posted Date: May 25, 2023
• Actual Study Start Date: March 4, 2020
• Estimated Primary Completion Date: February 21, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 15, 2022)

• Investigator-Assessed Progression-Free Survival (PFS) in the Primary Analysis Set [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 59 months) ]
• Overall Survival (OS) in the Primary Analysis Set [ Time Frame: From randomization to death from any cause (up to approximately 59 months) ]
• Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to approximately 59 months ]
• Percentage of Participants With Cytokine-Release Syndrome (CRS) [ Time Frame: Up to approximately 59 months ]

Original Primary Outcome Measures (submitted: March 2, 2020)

• Progression-Free Survival (PFS) [ Time Frame: From randomization up to disease progression or relapse or death (whichever occurs first), up to 59 months ]
• Overall Survival (OS) [ Time Frame: From randomization up to death of any cause, up to 59 months ]

Current Secondary Outcome Measures (submitted: December 15, 2022)

• Investigator-Assessed PFS in the Secondary Analysis Set [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 59 months) ]
• OS in the Secondary Analysis Set [ Time Frame: From randomization to death from any cause (up to approximately 59 months) ]
• Investigator-Assessed Confirmed Objective Response Rate (ORR) [ Time Frame: From randomization up to approximately 59 months ]
• Investigator-Assessed Duration of Response (DOR) [ 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 approximately 59 months) ]
• Investigator-Assessed PFS Rates at 6 Months and 12 Months [ Time Frame: 6 months, 12 months ]
• OS Rates at 12 Months and 24 Months [ 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 [ Time Frame: From randomization until the first confirmed clinically meaningful deterioration (up to approximately 59 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.

Original Secondary Outcome Measures (submitted: March 2, 2020)

• Confirmed Overall Response Rate (ORR) [ Time Frame: From randomization up to disease progression or relapse or death (whichever occurs first), up to 59 months ]
• Duration of Response (DOR) [ Time Frame: From randomization up to disease progression or relapse or death (whichever occurs first), up to 59 months ]
• PFS Rates at 6 Months and 12 Months [ Time Frame: 6 months, 12 months ]
• OS 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 59 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.
• PFS in Participants With Programmed Death-Ligand 1 (PD-L1) Expression [ Time Frame: From randomization up to disease progression or relapse or death (whichever occurs first), up to 59 months ]
• OS in Participants With PD-L1 Expression [ Time Frame: From randomization up to death of any cause, up to 59 months ]
• Percentage of Participants With Adverse Events (AEs) [ Time Frame: Up to 59 months ]
• Minimum Serum Concentration (Cmin) of Tiragolumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at treatment discontinuation (TD) visit (up to 59 months) ]
• Maximum Serum Concentration (Cmax) of Tiragolumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 59 months) ]
• Cmin of Atezolizumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 59 months) ]
• Cmax of Atezolizumab [ Time Frame: Predose and postdose on Day 1 of Cycle 1 (cycle=21 days) and predose on Day 1 of Cycles 2, 3, 4, 8,12 and 16 and at TD visit (up to 59 months) ]
• Percentage of Participants With Anti-drug Antibodies (ADAs) to Tiragolumab [ Time Frame: Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8,12 and 16 and at TD visit (up to 59 months) ]
• Percentage of Participants With ADAs to Atezolizumab [ Time Frame: Predose on Day 1 of Cycles (cycle=21 days) 1, 2, 3, 4, 8,12 and 16 and at TD visit (up to 59 months) ]

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

Descriptive Information

• Brief Title: A Study of Tiragolumab in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer
• Official Title: A Phase III, Randomized, Double-Blinded, Placebo-Controlled Study of Tiragolumab, an Anti-Tigit Antibody, in Combination With Atezolizumab Compared With Placebo in Combination With Atezolizumab in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic PD-L1-Selected Non-Small Cell Lung Cancer
• Brief Summary: The purpose of the study is to evaluate the efficacy and safety of tiragolumab plus atezolizumab compared with placebo plus atezolizumab in participants with previously untreated locally advanced, unresectable or metastatic PD-L1-selected non-small cell lung cancer (NSCLC), with no epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) translocation. Eligible participants will be randomized in a 1:1 ratio to receive either tiragolumab plus atezolizumab or placebo plus atezolizumab.
• 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: Non-Small Cell Lung Cancer

Intervention

• Drug: Atezolizumab
  Atezolizumab 1200 milligrams (mg) administered by intravenous (IV) infusion Q3W on Day 1 of each 21-day cycle.
  Other Name: Tecentriq
• Drug: Tiragolumab
  Tiragolumab 600 mg administered by IV infusion Q3W on Day 1 of each 21-day cycle.
  Other Name: MTIG7192A
• Drug: Matching Placebo
  Matching Placebo administered by IV infusion Q3W on Day 1 of each 21-day cycle.

Study Arms

• Experimental: Tiragolumab + Atezolizumab
  Participants will receive atezolizumab followed by tiragolumab every 3 weeks (Q3W) on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Tiragolumab
• Placebo Comparator: Placebo + Atezolizumab
  Participants will receive atezolizumab followed by placebo Q3W on Day 1 of each 21-day cycle until disease progression, loss of clinical benefit or unacceptable toxicity.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Matching Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 15, 2022): 660
• Original Estimated Enrollment (submitted: March 2, 2020): 500
• Estimated Study Completion Date: February 21, 2025
• Estimated Primary Completion Date: February 21, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Histologically or cytologically documented locally advanced or recurrent NSCLC not eligible for curative surgery and/or definitive radiotherapy with or without chemoradiotherapy, or metastatic Stage IV non-squamous or squamous NSCLC
• No prior systemic treatment for metastatic NSCLC
• High tumor tissue PD-L1 expression
• Measurable disease per Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
• Adequate hematologic and end-organ function
• For participants enrolled in the extended China enrollment phase: current resident of mainland China or Taiwan and of Chinese ancestry.

Exclusion Criteria:

• Known mutation in the EGFR gene or an ALK fusion oncogene
• Symptomatic, untreated, or actively progressing central nervous system metastases
• 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
• Malignancies other than NSCLC within 5 years, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
• Severe infection within 4 weeks prior to initiation of study treatment
• Positive test result for human immunodeficiency virus (HIV)
• Active hepatitis B or hepatitis C
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, 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 initiation of study treatment.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: GO41717 https://forpatients.roche.com/; 888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

• Listed Location Countries: Argentina, Australia, Austria, Brazil, China, Denmark, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Peru, Poland, Russian Federation, Serbia, Spain, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United States

Administrative Information

• NCT Number: NCT04294810
• Other Study ID Numbers: GO41717; 2019-002925-31 ( 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 Trial; Hoffmann-La Roche

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