A Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Participants With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC) (SKYSCRAPER-03)

• ClinicalTrials.gov Identifier: NCT04513925
• Recruitment Status: Active, not recruiting
• First Posted: August 14, 2020
• Last Update Posted: May 22, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: August 13, 2020
• First Posted Date: August 14, 2020
• Last Update Posted Date: May 22, 2023
• Actual Study Start Date: August 24, 2020
• Estimated Primary Completion Date: October 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 26, 2023)

• Independent Review Facility (IRF)-assessed Progression Free Survival (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 approximately 90 months) ]
• IRF-assessed PFS in the PD-L1-positive Analysis Set (PPAS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 90 months) ]

• Original Primary Outcome Measures (submitted: August 13, 2020): Independent Review Facility (IRF) Assessed Progression Free Survival (PFS) [ Time Frame: From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 90 months) ]

Current Secondary Outcome Measures (submitted: January 26, 2023)

• Overall Survival (OS) in the FAS [ Time Frame: From randomization to death from any cause (up to approximately 90 months) ]
• Investigator-assessed PFS in the FAS [ Time Frame: Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 90 months) ]
• IRF-assessed Confirmed Objective Response Rate (ORR) in the FAS [ Time Frame: From randomization up to approximately 90 months ]
• Investigator-assessed Confirmed ORR in the FAS [ Time Frame: From randomization up to approximately 90 months ]
• IRF-assessed Duration of Response (DOR) in the FAS [ Time Frame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 90 months) ]
• Investigator-assessed DOR in the FAS [ Time Frame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 90 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 FAS [ Time Frame: Up to approximately 90 months ]
  TTCD 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.
• OS in the PPAS [ Time Frame: From randomization to death from any cause (up to approximately 90 months) ]
• Investigator-assessed PFS in the PPAS [ Time Frame: Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 90 months) ]
• IRF-assessed Confirmed ORR in the PPAS [ Time Frame: From randomization up to approximately 90 months ]
• Investigator-assessed Confirmed ORR in the PPAS [ Time Frame: From randomization up to approximately 90 months ]
• IRF-assessed DOR in the PPAS [ Time Frame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 90 months) ]
• Investigator-assessed DOR in the PPAS [ Time Frame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 90 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 PPAS [ Time Frame: Up to approximately 90 months ]
  TTCD 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.
• IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months [ Time Frame: 12, 18 and 24 months ]
• Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months [ Time Frame: 12, 18 and 24 months ]
• OS Rates at 12 Months, 24 Months, 36 Months and 48 Months [ Time Frame: 12, 24, 36 and 48 months ]
• Investigator-assessed Time to Death or Distant Metastasis (TTDM) [ Time Frame: From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 90 months) ]
• Percentage of Participants With Adverse Events [ Time Frame: Up to approximately 90 months ]

Original Secondary Outcome Measures (submitted: August 13, 2020)

• Overall Survival (OS) [ Time Frame: From randomization to death from any cause (up to approximately 90 months) ]
• Investigator-assessed PFS [ Time Frame: Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 90 months) ]
• Confirmed Overall Response Rate (ORR) [ Time Frame: From randomization up to approximately 90 months ]
• Duration of Response (DOR) [ Time Frame: From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 90 months) ]
• PFS Rates at 12 Months, 18 Months and 24 Months [ Time Frame: 12, 18 and 24 months ]
• OS Rates at 12 Months, 24 Months, 36 Months and 48 Months [ Time Frame: 12, 24, 36 and 48 months ]
• Time to Death or Distant Metastasis (TTDM) [ Time Frame: From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 90 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: Up to approximatley 90 months ]
  TTCD 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 90 approximately months ]
• Serum Concentration of Tiragolumab [ Time Frame: Pre-dose and post-dose on Day 1 of Cycles 1 and 3 (cycle=28 days) and predose on Day 1 of Cycles 2, 4, 8, 10 and 12 and at treatment discontinuation (TD) visit (up to approximately 90 months) ]
• Serum Concentration of Atezolizumab [ Time Frame: Pre-dose and post-dose on Day 1 of Cycle 1 (cycle=28 days) and predose on Day 1 of Cycles 2, 3, 4, 8, 10 and 12 and at TD visit (up to approximately 90 months) ]
• Percentage of Participants With Anti-Drug Antibodies (ADAs) to Tiragolumab [ Time Frame: Predose on Day 1 of Cycles 2, 3, 4, 8, 10 and 12 (cycle=28 days) and at TD visit (up to approximately 90 months) ]
• Percentage of Participants With ADAs to Atezolizumab [ Time Frame: Predose on Day 1 of Cycles 2, 3, 4, 8, 10 and 12 (cycle=28 days) and at TD visit (up to approximately 90 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 and Tiragolumab Compared With Durvalumab in Participants With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer (NSCLC)
• Official Title: A Phase III, Open-Label, Randomized Study of Atezolizumab and Tiragolumab Compared With Durvalumab in Patients With Locally Advanced, Unresectable Stage III Non-Small Cell Lung Cancer Who Have Not Progressed After Concurrent Platinum-Based Chemoradiation
• Brief Summary: The purpose of this study is to evaluate the efficacy and safety of atezolizumab in combination with tiragolumab compared with durvalumab in participants with locally advanced, unresectable Stage III non-small cell lung cancer (NSCLC) who have received at least two cycles of concurrent platinum-based chemoradiotherapy (CRT) and have not had radiographic disease progression.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Non-small Cell Lung Cancer (NSCLC)

Intervention

• Drug: Atezolizumab
  Atezolizumab 1680 mg every 4 weeks (Q4W) will be administered IV on Day 1 of each 28-day cycle.
  Other Name: Tecentriq; RO5541267
• Drug: Tiragolumab
  Tiragolumab 840 mg Q4W will be administered IV on Day 1 of each 28-day cycle.
  Other Name: MTIG7192A; RO7092284
• Drug: Durvalumab
  Durvalumab will be administered based on weight at 10 mg/kg IV every 2 weeks (Q2W) on Days 1 and 15 of each 28-day cycle, or will be administered at a fixed dose of 1500 mg IV every 4 weeks (Q4W) (for participants whose weight >/= 30 kg) on Day 1 of each 28-day cycle.

Study Arms

• Experimental: Atezolizumab + Tiragolumab
  Participants will receive atezolizumab administered intravenously (IV) on Day 1 of each 28-day cycle followed by tiragolumab administered IV on Day 1 of each 28-day cycle for a maximum of 13 cycles.
  Interventions:

  • Drug: Atezolizumab
  • Drug: Tiragolumab
• Active Comparator: Durvalumab
  Participants will receive durvalumab administered IV during each 28-day cycle for a maximum of 13 cycles.
  Intervention: Drug: Durvalumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 19, 2023): 829
• Original Estimated Enrollment (submitted: August 13, 2020): 800
• Estimated Study Completion Date: December 30, 2027
• Estimated Primary Completion Date: October 30, 2024 (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 NSCLC with locally advanced, unresectable Stage III NSCLC of either squamous or non-squamous histology
• Whole-body Positron Emission Tomography-Computed Tomography (PET-CT) scan, performed prior and within 42 days of the first dose of concurrent chemoradiotherapy (cCRT)
• At least two prior cycles of platinum-based chemotherapy administered concurrently with radiotherapy (RT), which must be completed within 1 to 42 days prior to randomization in the study (one cycle of cCRT is defined as 21 or 28 days)
• The radiotherapy (RT) component in the cCRT must have been at a total dose of radiation of 60 (±10 percent [%]) gray (Gy) (54 Gy to 66 Gy) administered by intensity modulated RT (preferred) or 3D-conforming technique
• No progression during or following concurrent platinum-based CRT
• A known PD-L1 result
• Life expectancy >/= 12 weeks
• Adequate hematologic and end-organ function
• Female participants must be willing to avoid pregnancy for 90 days after the final dose of tiragolumab and 5 months after the final dose of atezolizumab, or for 3 months after the final dose of durvalumab
• Male participants must remain abstinent or use a condom during the treatment period and for 90 days after the final dose of tiragolumab
• Male participants must not donate sperm during the treatment period and for 90 days after the final dose of tiragolumab

Exclusion Criteria:

• Any history of prior NSCLC and/or any history of prior treatment for NSCLC (participants must be newly diagnosed with unresectable Stage III disease)
• NSCLC known to have a mutation in the epidermal growth factor receptor (EGFR) gene or an anaplastic lymphoma kinase (ALK) fusion oncogene
• Any evidence of Stage IV disease
• Treatment with sequential CRT for locally advanced NSCLC
• Participants with locally advanced NSCLC who have progressed during or after the definitive cCRT prior to randomization
• Any Grade >2 unresolved toxicity from previous CRT
• Grade >= 2 pneumonitis from prior CRT
• 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
• History of malignancy other than NSCLC within 5 years prior to screening with the exception of malignancies with a negligible risk of metastasis or death
• Prior allogeneic stem cell or solid organ transplantation
• Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
• Treatment with investigational therapy within 28 days prior to initiation of study treatment
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein 4, anti-T-cell immunoreceptor with Ig and ITIM domains (anti-TIGIT), anti-PD-1 and anti-PD-L1
• Any prior Grade >/= 3 immune-mediated adverse event or any unresolved Grade > 1 immune-mediated adverse event while receiving any previous immunotherapy agent other than immune checkpoint blockade agents
• Treatment with systemic immunosuppressive medication
• Women who are pregnant, or breastfeeding

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: Argentina, Australia, Austria, Belgium, Brazil, Canada, China, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
• Removed Location Countries: Czechia

Administrative Information

• NCT Number: NCT04513925
• Other Study ID Numbers: GO41854; 2019-004773-29 ( 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