Carcinoma, Non-Small-Cell Lung
Conditions
Brief summary
The main purpose of the study is to examine if periadjuvant (neoadjuvant, then adjuvant) immunotherapy will prolong event free survival in participants with early stage non-small cell lung cancer.
Interventions
BIOLOGICALNivolumab
Specified dose on specified days
DRUGCarboplatin
Specified dose on specified days
DRUGCisplatin
Specified dose on specified days
DRUGPaclitaxel
Specified dose on specified days
DRUGPemetrexed
Specified dose on specified days
DRUGPlacebo
Specified dose on specified days
DRUGDocetaxel
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with suspected or histologically confirmed Stage IIA (\> 4 cm) to IIIB (T3N2) non-small cell lung carcinoma (NSCLC) with disease that is considered resectable * No brain metastasis * Treatment-naive for NSCLC (no prior systemic anti-cancer treatment) * Ability to provide surgical or biopsy tumor tissue for biomarkers * Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1
Exclusion criteria
* Participants with an active, known or suspected autoimmune disease * Any positive test for hepatitis B virus or hepatitis C virus or human immunodeficiency virus (HIV) * Any previous anti-cancer treatment including cytotoxic, IO treatment, targeted agents, or radiotherapy for NSCLC * Prior treatment with any anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) by BICR | From randomization to disease progression, worsening, recurrence, or death due to any cause (up to approximately 44 months) | The length of time from randomization to any of the following events: progression of disease or worsening of disease precluding surgery, if surgery is attempted but gross resection is abandoned due to unresectable tumor or worsening of disease, progression or recurrence of disease after surgery, progression or recurrence of disease without surgery, or death due to any cause. Progression/recurrence will be assessed by BICR per RECIST 1.1. Participants who do not undergo surgery for reason other than progression will be considered to have an event at RECIST 1.1 progression or death |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization and the date of death due to any cause. | OS is defined as the time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive. |
| Pathologic Complete Response (pCR) Rate | From randomization up to approximately 44 months | Pathologic complete response (pCR) rate is defined as the percentage of randomized participants with absence of residual viable tumor in lung and lymph nodes as evaluated by blinded independent pathology review (BIPR). |
| Major Pathological Response (MPR) Rate | From randomization up to approximately 44 months | Major pathological response (MPR) rate is defined as the percentage of randomized participants with ≤10% residual viable tumor in lung and lymph nodes as evaluated by blinded independent pathology review (BIPR). |
| The Number of Participants With Adverse Events (AEs) | From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| The Number of Participants With Serious Adverse Events (SAEs) | From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months) | Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event. |
| The Number of Participants With Select Adverse Events (AEs) | From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months) | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Select AEs include endocrinopathies, diarrhea/colitis, hepatitis, pneumonitis, interstitial nephritis, and rash. Multiple event terms that may describe each of these were grouped into endocrine, GI, hepatic, pulmonary, renal, and skin select AE categories, respectively. Hypersensitivity/infusion reactions were analyzed along with the select AE categories. |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czechia, France, Germany, Ireland, Italy, Japan, Mexico, Netherlands, Poland, Puerto Rico, Romania, Russia, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab + SOC Chemotherapy Nivolumab 360 mg Q3W + SOC platinum-based doublet chemotherapy Q3W x 4 cycles as neoadjuvant treatment followed by surgery; then post surgery nivolumab 480 mg Q4W adjuvant treatment for up to 13 cycles (approximately 1 year) | 229 |
| Placebo + SOC Chemotherapy Placebo Q3W + SOC platinum-based doublet chemotherapy Q3W x 4 cycles as neoadjuvant treatment followed by surgery, then post-surgery placebo Q4W for up to 13 cycles (approximately 1 year). | 232 |
| Total | 461 |
Baseline characteristics
| Characteristic | Nivolumab + SOC Chemotherapy | Placebo + SOC Chemotherapy | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 127 Participants | 132 Participants | 259 Participants |
| Age, Categorical Between 18 and 65 years | 102 Participants | 100 Participants | 202 Participants |
| Age, Continuous | 64.2 Years STANDARD_DEVIATION 7.9 | 64.6 Years STANDARD_DEVIATION 8.4 | 64.4 Years STANDARD_DEVIATION 8.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 17 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 128 Participants | 113 Participants | 241 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 92 Participants | 102 Participants | 194 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 66 Participants | 50 Participants | 116 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 3 Participants | 7 Participants |
| Race (NIH/OMB) White | 155 Participants | 175 Participants | 330 Participants |
| Sex: Female, Male Female | 62 Participants | 72 Participants | 134 Participants |
| Sex: Female, Male Male | 167 Participants | 160 Participants | 327 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 40 / 229 | 48 / 232 |
| other Total, other adverse events | 214 / 228 | 212 / 230 |
| serious Total, serious adverse events | 109 / 228 | 83 / 230 |
Outcome results
Primary
Event-Free Survival (EFS) by BICR
The length of time from randomization to any of the following events: progression of disease or worsening of disease precluding surgery, if surgery is attempted but gross resection is abandoned due to unresectable tumor or worsening of disease, progression or recurrence of disease after surgery, progression or recurrence of disease without surgery, or death due to any cause. Progression/recurrence will be assessed by BICR per RECIST 1.1. Participants who do not undergo surgery for reason other than progression will be considered to have an event at RECIST 1.1 progression or death
Time frame: From randomization to disease progression, worsening, recurrence, or death due to any cause (up to approximately 44 months)
Population: All randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab + SOC Chemotherapy | Event-Free Survival (EFS) by BICR | NA Months |
| Placebo + SOC Chemotherapy | Event-Free Survival (EFS) by BICR | 18.43 Months |
p-value: 0.0002595% CI: [0.43, 0.78]Log Rank
Secondary
Major Pathological Response (MPR) Rate
Major pathological response (MPR) rate is defined as the percentage of randomized participants with ≤10% residual viable tumor in lung and lymph nodes as evaluated by blinded independent pathology review (BIPR).
Time frame: From randomization up to approximately 44 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab + SOC Chemotherapy | Major Pathological Response (MPR) Rate | 35.4 Percentage of participants |
| Placebo + SOC Chemotherapy | Major Pathological Response (MPR) Rate | 12.1 Percentage of participants |
95% CI: [15.8, 30.6]
95% CI: [2.48, 6.49]
Secondary
Overall Survival (OS)
OS is defined as the time between the date of randomization and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive.
Time frame: From randomization and the date of death due to any cause.
Secondary
Pathologic Complete Response (pCR) Rate
Pathologic complete response (pCR) rate is defined as the percentage of randomized participants with absence of residual viable tumor in lung and lymph nodes as evaluated by blinded independent pathology review (BIPR).
Time frame: From randomization up to approximately 44 months
Population: All randomized participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab + SOC Chemotherapy | Pathologic Complete Response (pCR) Rate | 25.3 Percentage of Participants |
| Placebo + SOC Chemotherapy | Pathologic Complete Response (pCR) Rate | 4.7 Percentage of Participants |
95% CI: [14.3, 26.6]
95% CI: [3.4, 12.97]
Secondary
The Number of Participants With Adverse Events (AEs)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months)
Population: All participants who received at least one dose of study medication in neoadjuvant or adjuvant setting.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nivolumab + SOC Chemotherapy | The Number of Participants With Adverse Events (AEs) | 222 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Adverse Events (AEs) | 225 Participants |
Secondary
The Number of Participants With Select Adverse Events (AEs)
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. Select AEs include endocrinopathies, diarrhea/colitis, hepatitis, pneumonitis, interstitial nephritis, and rash. Multiple event terms that may describe each of these were grouped into endocrine, GI, hepatic, pulmonary, renal, and skin select AE categories, respectively. Hypersensitivity/infusion reactions were analyzed along with the select AE categories.
Time frame: From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months)
Population: All participants who received at least one dose of study medication in neoadjuvant or adjuvant setting.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nivolumab + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Endocrine Event | 42 Participants |
| Nivolumab + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Pulmonary Event | 17 Participants |
| Nivolumab + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Gastrointestinal Event | 37 Participants |
| Nivolumab + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Renal Event | 34 Participants |
| Nivolumab + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Skin Event | 71 Participants |
| Nivolumab + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction Event | 15 Participants |
| Nivolumab + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Hepatic Event | 46 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Skin Event | 53 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Hepatic Event | 31 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Renal Event | 18 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Endocrine Event | 13 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Hypersensitivity/Infusion Reaction Event | 14 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Gastrointestinal Event | 37 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Select Adverse Events (AEs) | Pulmonary Event | 8 Participants |
Secondary
The Number of Participants With Serious Adverse Events (SAEs)
Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is an important medical event.
Time frame: From first treatment to 30 days after last treatment of study therapy including definitive surgery and radiotherapy (up to approximately 28 months)
Population: All participants who received at least one dose of study medication in neoadjuvant or adjuvant setting.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nivolumab + SOC Chemotherapy | The Number of Participants With Serious Adverse Events (SAEs) | 96 Participants |
| Placebo + SOC Chemotherapy | The Number of Participants With Serious Adverse Events (SAEs) | 71 Participants |