Cancer
Conditions
Brief summary
The purpose of this study is to determine whether nivolumab is an effective treatment for cancer that has advanced or has spread. Various tumor types may be eligible for enrollment.
Interventions
BIOLOGICALNivolumab
Specified dose on specified days
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
* Diagnosed with advanced or metastatic malignancy * Received standard of care treatment for primary malignancy and standard of care treatment for relapsed cancer * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Exclusion criteria
* Prior treatment with an antiPD1, antiPDL1, antiPDL2, antiCD137, or antiCTLA4 antibody, or any other antibody or drug specifically targeting Tcell co-stimulation or checkpoint pathways. * Subjects previously treated with investigational anticancer therapies less than 6 weeks prior to the first dose of Nivolumab * Subjects with an active, known, or suspected autoimmune disease Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | From first dose to the date of objectively documented progression (per tumor-specific response criteria) or the date of subsequent therapy, whichever occurs first (up to approximately 24 months) | ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR). Best overall response is defined as the best response designation, as determined by investigator, recorded in the specified timeframe, according to the RECIST 1.1 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Objective Response (TTR) | From the first dosing date to the date of the first confirmed response (up to approximately 10 months) | TTR is defined as the time from first dosing date to the date of the first confirmed response (Complete Response, CR or Partial Response, PR), as assessed by investigator. |
| Clinical Benefit Rate (CBR) | From the first dosing date to the date of the last dose (approximately 24 months) | CBR is defined as the percentage of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) or Stable Disease (SD). |
| Overall Survival Rate at 1 Year | From the first dosing date to 1 year later | Overall Survival (OS) is defined as the time from the first dosing date to the date of death. A participant who has not died will be censored at last known date alive. OS rate at 1 year is measured as the percent of participants still alive at 1 year after first dosing, measured from Kaplan-Meier curve of OS. |
| Number of Participants Who Died | From first dose to 100 days following last dose (up approximately 27 months) | Number of participants who died for any cause |
| Number of Participants Experiencing Adverse Events (AEs) | From first dose to 30 days following the last dose (up to approximately 25 months) | Number of participants who experienced any grade, any cause AEs |
| Number of Participants Experiencing Serious Adverse Events (SAEs) | From first dose to 100 days following the last dose (up to approximately 27 months) | Number of participants who experienced any grade, any cause SAEs |
| Duration of Response (DOR) | From the time of first confirmed response to the date of the first documented progression (up to approximately 22 months) | DOR is defined as the time from first confirmed response (Complete Response, CR or Partial Response, PR) to the date of the first documented tumor progression (as determined by investigator) or death due to any cause, whichever occurs first. Median DOR computed using Kaplan-Meier method |
| Number of Participants Experiencing Immune-mediated Adverse Events (IMAEs) | From first dose to 100 days following the last dose (up to approximately 27 months) | Number of participants who experienced IMAEs. IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity. |
| Number of Participants Experiencing Select Adverse Events | From first dose to 30 days following the last dose (up to approximately 25 months) | Number of participants who experienced Select Adverse Events. Select Adverse Events categories include: gastrointestinal, hepatic, pulmonary, renal, skin, hypersensitivity/infusion reaction. |
| Number of Participants Experiencing Adverse Events (AEs) Leading to Dose Delay or Dose Reduction | From first dose to 30 days following the last dose (up to approximately 25 months) | Number of participants who experienced AEs leading to dose delay or dose reduction. A dose will be considered as delayed if the delay is exceeding 3 days after the intended dose date (i.e., greater than or equal to 4 days from scheduled dosing date) |
| Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | From first dose to 30 days following the last dose (up to approximately 25 months) | Number of participants who experienced the laboratory abnormalities in specific liver tests described in the individual categories. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal |
| Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | From first dose to 100 days following the last dose (up to approximately 27 months) | Number of participants who experienced the laboratory abnormalities in specific thyroid tests described in the individual categories. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal |
| Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | From first dose to 30 days following the last dose (up to approximately 25 months) | Number of participants who experienced AEs leading to discontinuation of study therapy |
Countries
Germany, United States
Participant flow
Pre-assignment details
239 participants were treated.
Participants by arm
| Arm | Count |
|---|---|
| Advanced Malignancies Cohort Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W | 239 |
| Total | 239 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Transition From Period 1 to Period 2 | Death | 2 |
| Transition From Period 1 to Period 2 | Lost to Follow-up | 3 |
| Transition From Period 1 to Period 2 | Other reasons | 1 |
| Transition From Period 1 to Period 2 | Participant withdrew consent | 1 |
| Treatment Period 1 | Adverse event unrelated to study drug | 12 |
| Treatment Period 1 | Death | 2 |
| Treatment Period 1 | Disease progression | 90 |
| Treatment Period 1 | No longer meet study criteria | 1 |
| Treatment Period 1 | Other reasons | 6 |
| Treatment Period 1 | Participant request to discontinue | 9 |
| Treatment Period 1 | Participant withdrew consent | 3 |
| Treatment Period 1 | Study Drug Toxicity | 6 |
| Treatment Period 2 | Adverse event unrelated to study drug | 1 |
| Treatment Period 2 | Disease progression | 69 |
| Treatment Period 2 | Maximum clinical benefit | 1 |
| Treatment Period 2 | Other reasons | 3 |
| Treatment Period 2 | Participant request to discontinue | 2 |
| Treatment Period 2 | Participant withdrew consent | 3 |
| Treatment Period 2 | Study Drug Toxicity | 5 |
Baseline characteristics
| Characteristic | Advanced Malignancies Cohort |
|---|---|
| Age, Continuous | 59.2 Years STANDARD_DEVIATION 13.79 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 158 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 70 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants |
| Race (NIH/OMB) White | 203 Participants |
| Sex: Female, Male Female | 148 Participants |
| Sex: Female, Male Male | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 156 / 239 |
| other Total, other adverse events | 216 / 239 |
| serious Total, serious adverse events | 148 / 239 |
Outcome results
Primary
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR). Best overall response is defined as the best response designation, as determined by investigator, recorded in the specified timeframe, according to the RECIST 1.1 criteria.
Time frame: From first dose to the date of objectively documented progression (per tumor-specific response criteria) or the date of subsequent therapy, whichever occurs first (up to approximately 24 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Malignancies Cohort | Objective Response Rate (ORR) | 7.9 Percent of Participants |
Secondary
Clinical Benefit Rate (CBR)
CBR is defined as the percentage of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) or Stable Disease (SD).
Time frame: From the first dosing date to the date of the last dose (approximately 24 months)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Malignancies Cohort | Clinical Benefit Rate (CBR) | 49.8 Percent of participants |
Secondary
Duration of Response (DOR)
DOR is defined as the time from first confirmed response (Complete Response, CR or Partial Response, PR) to the date of the first documented tumor progression (as determined by investigator) or death due to any cause, whichever occurs first. Median DOR computed using Kaplan-Meier method
Time frame: From the time of first confirmed response to the date of the first documented progression (up to approximately 22 months)
Population: All Responders (Participants with a confirmed CR or PR)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Advanced Malignancies Cohort | Duration of Response (DOR) | 21.78 Months |
Secondary
Number of Participants Experiencing Adverse Events (AEs)
Number of participants who experienced any grade, any cause AEs
Time frame: From first dose to 30 days following the last dose (up to approximately 25 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Experiencing Adverse Events (AEs) | 234 Participants |
Secondary
Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Number of participants who experienced AEs leading to discontinuation of study therapy
Time frame: From first dose to 30 days following the last dose (up to approximately 25 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation | 41 Participants |
Secondary
Number of Participants Experiencing Adverse Events (AEs) Leading to Dose Delay or Dose Reduction
Number of participants who experienced AEs leading to dose delay or dose reduction. A dose will be considered as delayed if the delay is exceeding 3 days after the intended dose date (i.e., greater than or equal to 4 days from scheduled dosing date)
Time frame: From first dose to 30 days following the last dose (up to approximately 25 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Experiencing Adverse Events (AEs) Leading to Dose Delay or Dose Reduction | 61 Participants |
Secondary
Number of Participants Experiencing Immune-mediated Adverse Events (IMAEs)
Number of participants who experienced IMAEs. IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.
Time frame: From first dose to 100 days following the last dose (up to approximately 27 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Experiencing Immune-mediated Adverse Events (IMAEs) | 8 Participants |
Secondary
Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests
Number of participants who experienced the laboratory abnormalities in specific liver tests described in the individual categories. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal
Time frame: From first dose to 30 days following the last dose (up to approximately 25 months)
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 3XULN | 11 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 5XULN | 8 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 10XULN | 3 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 20XULN | 1 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | TOTAL BILIRUBIN > 2XULN | 5 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 3XULN + BILIRUBIN > 2XULN WITHIN 1 DAY | 3 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests | ALT OR AST > 3XULN + BILIRUBIN > 2XULN WITHIN 30 DAYS | 3 Participants |
Secondary
Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests
Number of participants who experienced the laboratory abnormalities in specific thyroid tests described in the individual categories. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
Time frame: From first dose to 100 days following the last dose (up to approximately 27 months)
Population: All treated participants with available measurements
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN | 62 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH TSH <= ULN AT BASELINE | 42 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN | 12 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUE >= LLN | 0 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH > ULN WITH FT3/FT4 MISSING | 2 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN | 38 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH TSH >= LLN AT BASELINE | 25 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN | 8 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN | 1 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests | TSH < LLN WITH FT3/FT4 TEST MISSING | 1 Participants |
Secondary
Number of Participants Experiencing Select Adverse Events
Number of participants who experienced Select Adverse Events. Select Adverse Events categories include: gastrointestinal, hepatic, pulmonary, renal, skin, hypersensitivity/infusion reaction.
Time frame: From first dose to 30 days following the last dose (up to approximately 25 months)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Experiencing Select Adverse Events | Gastrointestinal Select AEs | 57 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Select Adverse Events | Hepatic Select AEs | 33 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Select Adverse Events | Pulmonary Select AEs | 6 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Select Adverse Events | Renal Select AEs | 22 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Select Adverse Events | Skin Select AEs | 59 Participants |
| Advanced Malignancies Cohort | Number of Participants Experiencing Select Adverse Events | Hypersensitivity/Infusion Reaction | 7 Participants |
Secondary
Number of Participants Experiencing Serious Adverse Events (SAEs)
Number of participants who experienced any grade, any cause SAEs
Time frame: From first dose to 100 days following the last dose (up to approximately 27 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Experiencing Serious Adverse Events (SAEs) | 148 Participants |
Secondary
Number of Participants Who Died
Number of participants who died for any cause
Time frame: From first dose to 100 days following last dose (up approximately 27 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Advanced Malignancies Cohort | Number of Participants Who Died | 72 Participants |
Secondary
Overall Survival Rate at 1 Year
Overall Survival (OS) is defined as the time from the first dosing date to the date of death. A participant who has not died will be censored at last known date alive. OS rate at 1 year is measured as the percent of participants still alive at 1 year after first dosing, measured from Kaplan-Meier curve of OS.
Time frame: From the first dosing date to 1 year later
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Advanced Malignancies Cohort | Overall Survival Rate at 1 Year | 56.1 Percent of participants |
Secondary
Time to Objective Response (TTR)
TTR is defined as the time from first dosing date to the date of the first confirmed response (Complete Response, CR or Partial Response, PR), as assessed by investigator.
Time frame: From the first dosing date to the date of the first confirmed response (up to approximately 10 months)
Population: All Responders (Participants with a confirmed CR or PR)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Advanced Malignancies Cohort | Time to Objective Response (TTR) | 3.54 Months | Standard Deviation 2.337 |