Squamous Cell Non-small Cell Lung Cancer
Conditions
Brief summary
The purpose of the study is to assess the objective response rate (change in tumor size from baseline) in patients with advanced or metastatic squamous cell nonsmall-cell lung cancer treated with Nivolumab (BMS-936558) after failure of 2 prior systemic regimens
Interventions
DRUGNivolumab
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Men and women ≥18 years of age * Patients with histologically or cytologically documented squamous cell nonsmall-cell lung cancer who present with Stage IIIB/Stage IV disease (according to version 7 of the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology), or with recurrent or progressive disease following multimodal therapy (radiation therapy, surgical resection, or definitive chemoradiation for locally advanced disease * Eastern Cooperative Oncology Group Performance Status of 0 or 1 * Disease progression or recurrence after both a platinum doublet-based chemotherapy regimen and at least 1 additional systemic therapy * Measurable disease by computed tomography scan/magnetic resonance imaging as per Response Evaluation Criteria in Solid Tumors, volume 1.1
Exclusion criteria
* Untreated central nervous system (CNS) metastases. Metastases have been treated and patients neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. In addition, patients must have stopped taking corticosteroids or be taking a stable or decreasing dose of ≤10 mg prednisone daily (or equivalent) * Carcinomatous meningitis * Active known or suspected autoimmune disease or interstitial lung disease * Prior treatment on either arm of study CA209-017 or CA184-104 * Prior therapy with anti-Programmed death-1 (anti-PD-1), anti-Programmed cell death ligand 1 (anti-PD-L1), anti-Programmed cell death ligand 2 (anti-PD-L2), anti-CD137, or anti-Cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways * A condition requiring systemic treatment with corticosteroids or other immunosuppressive medications within 14 days of first dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Assessed by Independent Radiology Review Committee (IRC) | Day 1 of treatment up to approximately 14 months | ORR is defined as the percentage of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) divided by the number of participants who received treatment. The IRC-assessed ORR (using RECIST v1.1, to confirm response and based on the IRC global radiology review after incorporation of on-study clinical data) was estimated using a binomial response rate and its corresponding 2-sided 95% exact confidence intervals using the Clopper-Pearson method. |
| Duration of Response (DOR) as Assessed by Independent Radiology Review Committee (IRC) | From the first treatment to the date of the first documented tumor progression or death. Approximately up to 14 months | DOR is defined as the time from first confirmed response (CR or PR) per IRC assessment to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Median values of DOR, along with two-sided 95% CI in each treatment group will be computed based on a log-log transformation method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) as Assessed by Investigator | Day 1 of treatment to approximately 101 months | ORR is defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on investigator assessment. The investigator-assessed ORR is summarized by a binomial response rate and its corresponding two-sided 95% exact CIs using Clopper-Pearson method. |
| Duration of Response (DOR) as Assessed by Investigator | From the first treatment to the date of the first documented tumor progression or death. Approximately up to 101 months | DOR is defined as the time from first confirmed response (CR or PR) per investigator assessment to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Median values of DOR, along with two-sided 95% CI in each treatment group will be computed based on a log-log transformation method. |
Countries
France, Germany, Italy, United States
Participant flow
Pre-assignment details
117 participants treated.
Participants by arm
| Arm | Count |
|---|---|
| Nivolumab, 3 mg/kg Participants received nivolumab, 3 mg/kg, intravenously over 60 minutes every 2 weeks (on Day 1 of each cycle) until disease progression, discontinuation due to toxicity, withdrawal of consent, or end of study. Every 2-week treatment period was considered to be a cycle. | 117 |
| Total | 117 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| End of Study Period | Death | 101 |
| End of Study Period | Lost to Follow-up | 1 |
| End of Study Period | Other Reasons | 10 |
| End of Study Period | Participant Withdrew Consent | 5 |
| Treatment Period | Adverse event unrelated to study drug | 11 |
| Treatment Period | Death | 1 |
| Treatment Period | Disease Progression | 85 |
| Treatment Period | Other Reasons | 3 |
| Treatment Period | Participant request to withdraw | 3 |
| Treatment Period | Study drug toxicity | 14 |
Baseline characteristics
| Characteristic | Nivolumab, 3 mg/kg |
|---|---|
| Age, Continuous | 64.1 Years STANDARD_DEVIATION 9.11 |
| Age, Customized 75 years and older | 16 Participants |
| Age, Customized At least 65 years and younger than 75 years | 43 Participants |
| Age, Customized Younger than 65 years | 58 Participants |
| Cell type Other | 0 Participants |
| Cell type Squamous cell carcinoma | 117 Participants |
| Central nervous system metastasis No | 115 Participants |
| Central nervous system metastasis Yes | 2 Participants |
| Disease stage Stage IIIB | 20 Participants |
| Disease stage Stage IV | 97 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 0 | 26 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 1 | 91 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 2 | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 3 | 0 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status 4 | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 69 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 48 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 11 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 99 Participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 85 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 108 / 117 |
| other Total, other adverse events | 110 / 117 |
| serious Total, serious adverse events | 88 / 117 |
Outcome results
Primary
Duration of Response (DOR) as Assessed by Independent Radiology Review Committee (IRC)
DOR is defined as the time from first confirmed response (CR or PR) per IRC assessment to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Median values of DOR, along with two-sided 95% CI in each treatment group will be computed based on a log-log transformation method.
Time frame: From the first treatment to the date of the first documented tumor progression or death. Approximately up to 14 months
Population: All confirmed responders per IRC
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab, 3 mg/kg | Duration of Response (DOR) as Assessed by Independent Radiology Review Committee (IRC) | 12 Months |
Primary
Objective Response Rate (ORR) as Assessed by Independent Radiology Review Committee (IRC)
ORR is defined as the percentage of participants with best overall response (OR) of confirmed complete response (CR) or partial response (PR) divided by the number of participants who received treatment. The IRC-assessed ORR (using RECIST v1.1, to confirm response and based on the IRC global radiology review after incorporation of on-study clinical data) was estimated using a binomial response rate and its corresponding 2-sided 95% exact confidence intervals using the Clopper-Pearson method.
Time frame: Day 1 of treatment up to approximately 14 months
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab, 3 mg/kg | Objective Response Rate (ORR) as Assessed by Independent Radiology Review Committee (IRC) | 14.5 Percentage of Participants |
Secondary
Duration of Response (DOR) as Assessed by Investigator
DOR is defined as the time from first confirmed response (CR or PR) per investigator assessment to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Median values of DOR, along with two-sided 95% CI in each treatment group will be computed based on a log-log transformation method.
Time frame: From the first treatment to the date of the first documented tumor progression or death. Approximately up to 101 months
Population: All treated participants who responded
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab, 3 mg/kg | Duration of Response (DOR) as Assessed by Investigator | 16.00 Months |
Secondary
Objective Response Rate (ORR) as Assessed by Investigator
ORR is defined as the percentage of treated participants with confirmed complete response (CR) or partial response (PR) per RECIST 1.1 based on investigator assessment. The investigator-assessed ORR is summarized by a binomial response rate and its corresponding two-sided 95% exact CIs using Clopper-Pearson method.
Time frame: Day 1 of treatment to approximately 101 months
Population: All Treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Nivolumab, 3 mg/kg | Objective Response Rate (ORR) as Assessed by Investigator | 15.4 Percentage of Participants |
Post Hoc
Duration of Response (DOR) as Assessed by Independent Radiology Review Committee (IRC)
DOR is defined as the time from first confirmed response (CR or PR) per IRC assessment to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. Participants who neither progress nor die will be censored on the date of their last evaluable tumor assessment. Median values of DOR, along with two-sided 95% CI in each treatment group will be computed based on a log-log transformation method.
Time frame: From the first treatment to the date of the first documented tumor progression or death. Approximately up to 21 months
Population: All confirmed responders per IRC
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Nivolumab, 3 mg/kg | Duration of Response (DOR) as Assessed by Independent Radiology Review Committee (IRC) | NA Months |