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)
Completion Date
Completion Date Type
Actual
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
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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 Description
PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 millimeters (mm) or unequivocal progression of existing non-target lesions. Kaplan-Meier (K-M) method was used to estimate median PFS.
Outcome Measure
Progression-free Survival (PFS), as Assessed by an Independent Review Facility (IRF) in Programmed Death-ligand 1 (PD-L1) Positive Analysis Set (PPAS)
Outcome Time Frame
From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Outcome Description
PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS.
Outcome Measure
PFS, as Assessed by an IRF in FAS
Outcome Time Frame
From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Secondary Ids
Secondary Id
2019-004773-29
Secondary Id
2019
Secondary Outcomes
Outcome Description
OS was defined as the time from randomization to death from any cause. K-M method was used to estimate median OS.
Outcome Time Frame
From randomization to death from any cause (up to approximately 57 months)
Outcome Measure
Overall Survival (OS) in PPAS
Outcome Description
PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS.
Outcome Time Frame
From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Outcome Measure
PFS, as Assessed by the Investigator in PPAS
Outcome Description
ORR was defined as the percentage of participants who achieved an objective response (OR), characterized by a complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by an IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesion \& normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
Confirmed Objective Response Rate (ORR), as Assessed by an IRF in PPAS
Outcome Description
ORR was defined as the percentage of participants who achieved an OR, characterized by CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
Confirmed ORR, as Assessed by the Investigator in PPAS
Outcome Description
DOR was defined as the time from the first occurrence of a confirmed OR, characterized by CR or PR, until the first date of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions \& normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Median DOR was estimated using the K-M method.
Outcome Time Frame
From first occurrence of a confirmed OR until the first date of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Outcome Measure
Duration of Response (DOR), as Assessed by an IRF in PPAS
Outcome Description
DOR was defined as the time from the first occurrence of a confirmed OR, characterized by CR or PR, until the first date of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Median DOR was estimated using the K-M method.
Outcome Time Frame
From first occurrence of a confirmed OR until the first date of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Outcome Measure
DOR, as Assessed by the Investigator in PPAS
Outcome Description
TTCD=time from randomization until first confirmed clinically meaningful deterioration (CCMD) on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Cough scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
Time to Confirmed Deterioration (TTCD) in Cough, as Assessed Using European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Lung Cancer Module (EORTC QLQ-LC13) in PPAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Dyspnoea was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in Dyspnoea, as Assessed Using EORTC QLQ-LC13 in PPAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Chest pain was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in Chest Pain, as Assessed Using EORTC QLQ-LC13 in PPAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, \& social), 3 symptom scales (fatigue, nausea, vomiting, \& pain), GHS/QoL, \& 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties). GHS/QoL questions were scored on 7-point scale with scores ranging from 1=Very poor to 7=Excellent. Scores were linearly transformed to a score range of 0-100. High score for GHS/QoL scale=better health-related quality-of-life (HRQoL). CCMD=decrease from baseline (≥10 points) in GHS/QoL scale score, held for at least 2 consecutive assessments/initial clinically meaningful decrease above baseline followed by death within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in Global Health Status (GHS)/Quality-of-life (QoL), as Assessed Using European Organisation for Research and Treatment of Cancer Quality-of-life Core-30 (EORTC QLQ-C30) in PPAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, \& social), 3 symptom scales (fatigue, nausea, vomiting, \& pain), GHS/QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties). PF was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to a score range of 0-100. High score for PF=high/healthy level of functioning. CCMD=decrease from baseline (≥10 points) in PF score, held for at least 2 consecutive assessments or initial clinically meaningful decrease above baseline followed by death within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in Physical Functioning (PF), as Assessed Using EORTC QLQ-C30 in PPAS
Outcome Description
OS was defined as the time from randomization to death from any cause. K-M method was used to estimate median OS.
Outcome Time Frame
From randomization to death from any cause (up to approximately 57 months)
Outcome Measure
OS in FAS
Outcome Description
PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS.
Outcome Time Frame
From randomization to first occurrence of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Outcome Measure
PFS, as Assessed by the Investigator in FAS
Outcome Description
ORR was defined as the percentage of participants who achieved an OR, characterized by CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by an IRF according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
Confirmed ORR, as Assessed by an IRF in FAS
Outcome Description
ORR was defined as the percentage of participants who achieved an OR, characterized by a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
Confirmed ORR, as Assessed by the Investigator in FAS
Outcome Description
DOR was defined as the time from the first occurrence of a confirmed OR, characterized by CR or PR, until the first date of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Median DOR was estimated using the K-M method.
Outcome Time Frame
From first occurrence of a confirmed OR until the first date of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Outcome Measure
DOR, as Assessed by an IRF in FAS
Outcome Description
DOR was defined as the time from the first occurrence of a confirmed OR, characterized by CR or PR, until the first date of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. CR was defined as disappearance of all target and non-target lesions, normalization of tumor marker level. Additionally, any lymph nodes (whether target or non-target) must have a reduction in short axis to \< 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. Median DOR was estimated using the K-M method.
Outcome Time Frame
From first occurrence of a confirmed OR until the first date of PD or death from any cause, whichever occurred first (up to approximately 57 months)
Outcome Measure
DOR, as Assessed by the Investigator in FAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Cough was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in Cough, as Assessed Using EORTC QLQ-LC13 in FAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Dyspnoea was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in Dyspnoea, as Assessed Using EORTC QLQ-LC13 in FAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-LC13 is a lung cancer-specific instrument consisting of 13 questions: one multiple-item scale assessing dyspnoea (3 items), and 10 single items assessing cough, hemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm or shoulder, pain in other parts, pain medication. Chest pain was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to score range of 0-100. High symptom score=high level of symptom severity. CCMD=increase from baseline (≥10 points) in a symptom score, held for at least two consecutive assessments or an initial clinically meaningful increase above baseline followed by death from any cause within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in Chest Pain, as Assessed Using EORTC QLQ-LC13 in FAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, \& social), 3 symptom scales (fatigue, nausea, vomiting, \& pain), GHS/QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties). GHS/QoL questions were scored on 7-point scale with scores ranging from 1=Very poor to 7=Excellent. Scores were linearly transformed to a score range of 0-100. High score for GHS/QoL scale=better HRQoL. CCMD=decrease from baseline (≥10 points) in GHS/QoL scale score, held for at least 2 consecutive assessments or initial clinically meaningful decrease above baseline followed by death within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in GHS/QoL, as Assessed Using EORTC QLQ-C30 in FAS
Outcome Description
TTCD=time from randomization until first CCMD on each respective score. EORTC QLQ-C30 is cancer-specific instrument consisting of 30 questions to evaluate 5 aspects of participant functioning (physical, emotional, role, cognitive, \& social), 3 symptom scales (fatigue, nausea, vomiting, \& pain), GHS/QoL, and 6 single items (dyspnea, insomnia, appetite loss, constipation, diarrhea \& financial difficulties). PF was scored on a 4-point scale: 1=Not at all, 2=A little, 3=Quite a bit, 4=Very much. Scores were linearly transformed to a score range of 0-100. High score for PF=high/healthy level of functioning. CCMD=decrease from baseline (≥10 points) in PF score, held for at least 2 consecutive assessments or initial clinically meaningful decrease above baseline followed by death within 6 weeks. K-M method was used to estimate median TTCD.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTCD in PF, as Assessed Using EORTC QLQ-C30 in FAS
Outcome Description
PFS rate at 12, 18, and 24 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by an IRF, at 12, 18, and 24 months. PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS rate. Percentages have been rounded off.
Outcome Time Frame
At Months 12, 18, and 24
Outcome Measure
PFS Rate at 12, 18, and 24 Months, as Assessed by an IRF in PPAS
Outcome Description
PFS rate at 12, 18, and 24 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by the investigator, at 12, 18, and 24 months. PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate median PFS rate. Percentages have been rounded off.
Outcome Time Frame
At Months 12, 18, and 24
Outcome Measure
PFS Rate at 12, 18, and 24 Months, as Assessed by the Investigator in PPAS
Outcome Description
OS rate at months 12, 24, 36 and 48 was defined as percentage of participants who did not experience death from any cause at the specified timepoints. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off.
Outcome Time Frame
At Months 12, 24, 36, and 48
Outcome Measure
OS Rate at 12, 24, 36, and 48 Months in PPAS
Outcome Description
TTDM was defined as the time from the date of randomization until the date of first documented distant metastasis, as assessed by investigator according to RECIST v1.1, or death, whichever occurred first. Distant metastasis was defined as any new lesion that was outside of the radiation field. K-M method was used to estimate median TTDM.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
Time-to-distant Metastasis (TTDM), as Assessed by the Investigator in PPAS
Outcome Description
PFS rate at 12, 18, and 24 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by an IRF, at 12, 18, and 24 months. PFS was defined as the time from randomization to the first occurrence of PD, as determined by an IRF according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate PFS rate. Percentages have been rounded off.
Outcome Time Frame
At Months 12, 18, and 24
Outcome Measure
PFS Rate at 12, 18, and 24 Months, as Assessed by an IRF in FAS
Outcome Description
PFS rate at 12, 18, and 24 months was defined as the percentage of participants who did not experience PD or death from any cause, as determined by the investigator, at 12, 18, and 24 months. PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest SOD at prior timepoints (including baseline). Additionally, the SOD must also demonstrate an absolute increase of ≥ 5 mm or unequivocal progression of existing non-target lesions. K-M method was used to estimate PFS rate. Percentages have been rounded off.
Outcome Time Frame
At Months 12, 18, and 24
Outcome Measure
PFS Rate at 12, 18, and 24 Months, as Assessed by the Investigator in FAS
Outcome Description
OS rate at months 12, 24, 36 and 48 was defined as percentage of participants who did not experience death from any cause at the specified timepoints. OS was defined as the time from randomization to death from any cause. K-M method was used to estimate OS rate. Percentages have been rounded off.
Outcome Time Frame
At Months 12, 24, 36, and 48
Outcome Measure
OS Rate at 12, 24, 36, and 48 Months in FAS
Outcome Description
TTDM was defined as the time from the date of randomization until the date of first documented distant metastasis, as assessed by investigator according to RECIST v1.1, or death, whichever occurred first. Distant metastasis was defined as any new lesion that was outside of the radiation field. K-M method was used to estimate median TTDM.
Outcome Time Frame
Up to approximately 57 months
Outcome Measure
TTDM, as Assessed by the Investigator in FAS
Outcome Description
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product.
Outcome Time Frame
Up to approximately 24.7 months
Outcome Measure
Number of Participants With Adverse Events (AEs)
Outcome Description
CRS=supraphysiologic response following administration of any immune therapy that results in activation/engagement of endogenous or infused T cells and/or other immune effector cells. Symptoms may be progressive, including fever at onset, and may also include hypotension, capillary leak (hypoxia), and end-organ dysfunction.
Outcome Time Frame
Up to approximately 24.7 months
Outcome Measure
Number of Participants With Cytokine Release Syndrome (CRS)
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
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
ATEZOLIZUMAB
TIRAGOLUMAB
DURVALUMAB