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.
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)
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Non-small Cell Lung Cancer (NSCLC)
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
* 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
Inclusion 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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04513925
Org Class
Industry
Org Full Name
Hoffmann-La Roche
Org Study Id
GO41854
Overall Status
Active, not recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
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
Primary Outcomes
Outcome Measure
Independent Review Facility (IRF)-assessed Progression Free Survival (PFS) in the PD-L1-positive Analysis Set (PPAS)
Outcome Time Frame
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
Outcome Measure
IRF-assessed PFS in the Full Analysis Set (FAS)
Outcome Time Frame
From randomization to the first occurrence of disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
Secondary Ids
Secondary Id
2019-004773-29
Secondary Outcomes
Outcome Time Frame
From randomization to death from any cause (up to approximately 114 months)
Outcome Measure
Overall Survival (OS) in the PPAS
Outcome Time Frame
Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 114 months)
Outcome Measure
Investigator-assessed PFS in the PPAS
Outcome Time Frame
From randomization up to approximately 114 months
Outcome Measure
IRF-assessed Confirmed Objective Response Rate (ORR) in the PPAS
Outcome Time Frame
From randomization up to approximately 114 months
Outcome Measure
Investigator-assessed Confirmed ORR in the PPAS
Outcome Time Frame
From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
Outcome Measure
IRF-assessed Duration of Response (DOR) in the PPAS
Outcome Time Frame
From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
Outcome Measure
Investigator-assessed DOR in the PPAS
Outcome Description
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.
Outcome Time Frame
Up to approximately 114 months
Outcome Measure
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
Outcome Time Frame
From randomization to death from any cause (up to approximately 114 months)
Outcome Measure
OS in the FAS
Outcome Time Frame
Time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first first (up to approximately 114 months)
Outcome Measure
Investigator-assessed PFS in the FAS
Outcome Time Frame
From randomization up to approximately 114 months
Outcome Measure
IRF-assessed Confirmed ORR in the FAS
Outcome Time Frame
From randomization up to approximately 114 months
Outcome Measure
Investigator-assessed Confirmed ORR in the FAS
Outcome Time Frame
From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
Outcome Measure
IRF-assessed DOR in the FAS
Outcome Time Frame
From first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to approximately 114 months)
Outcome Measure
Investigator-assessed DOR in the FAS
Outcome Description
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.
Outcome Time Frame
Up to approximately 114 months
Outcome Measure
TTCD Assessed Using EORTC QLQ-C30 Score in the FAS
Outcome Time Frame
12, 18 and 24 months
Outcome Measure
IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS
Outcome Time Frame
12, 18 and 24 months
Outcome Measure
IRF-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS
Outcome Time Frame
12, 18 and 24 months
Outcome Measure
Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the PPAS
Outcome Time Frame
12, 18 and 24 months
Outcome Measure
Investigator-assessed PFS Rates at 12 Months, 18 Months and 24 Months in the FAS
Outcome Time Frame
12, 24, 36 and 48 months
Outcome Measure
OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the PPAS
Outcome Time Frame
12, 24, 36 and 48 months
Outcome Measure
OS Rates at 12 Months, 24 Months, 36 Months and 48 Months in the FAS
Outcome Time Frame
From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 114 months)
Outcome Measure
Investigator-assessed Time to Death or Distant Metastasis (TTDM) in the PPAS
Outcome Time Frame
From randomization until the first date of distant metastasis or death in the absence of distant metastasis (up to approximately 114 months)
Outcome Measure
Investigator-assessed TTDM in the FAS
Outcome Time Frame
Up to approximately 114 months
Outcome Measure
Percentage of Participants With Adverse Events
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Haiying Cheng
Investigator Email
HCHENG@montefiore.org
Investigator Phone
718-405-8404