Solid Tumor
Conditions
Brief summary
The purpose of this study is to determine whether the combination of Ulocuplumab and Nivolumab is safe and effective in the treatment of pancreatic cancer and small cell lung cancer.
Detailed description
* Intervention model: Single group for Stage 1 DLT, then Parallel * Data Monitoring Committee: No (Stage 1) Yes (Stage 2 Randomized Ph2)
Interventions
DRUGUlocuplumab
DRUGNivolumab
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
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: * SCLC or PAC that is advanced or has spread to other parts of the body * Treated with at least one other chemotherapy that did not work or where cancer relapsed * Minimal limitations on activities of daily living as measured by Eastern Cooperative Oncology Group (ECOG) score of 0-1
Exclusion criteria
* Patients with cancer that spread to the brain * Active, known or suspected autoimmune disease * Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | From first dose until date of last dose of ulocuplumab or nivolumab plus 100 days (assessed up to January 2017, approximately 18 months) | The number participants who experienced on-study AEs, SAEs, and AEs requiring immune modulating medication is reported. |
| Objective Response Rate (ORR) Per RECIST 1.1 Criteria | From first dose until disease progression or treatment discontinuation (assessed up to January 2017, approximately 18 months) | ORR is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants. BOR is defined as the best response designation recorded between the first dose date and the date of progression per RECIST 1.1, or the date of subsequent anti-cancer therapy, whichever occurs first. CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)=At least a 20% increase in the sum of diameters of target lesions, referencing the smallest sum on study, and an absolute increase of at least 5 mm, or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referencing the smallest sum diameters while on study. |
| Overall Survival (OS) | From date of randomization to date of death (assessed up to study completion, approximately 18 months) | If a Phase 2 comparative study is initiated and, for PAC only: Overall Survival is defined as the time from randomization to date of death due to any cause. |
| Number of Participants With Laboratory Abnormalities | From first dose until date of last dose of ulocuplumab or nivolumab plus 100 days (assessed up to January 2017, approximately 18 months) | The number of participants who experienced on-study Grade 3 or 4 laboratory abnormalities (without Grade 3 or 4 abnormality at baseline) was reported for each arm. |
| Number of Participants With Electrocardiogram Abnormalities | From first dose to date of last dose plus 30 days | The number of participants experiencing electrocardiogram abnormalities was reported for each arm |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | From first dose to date of progression (assessed up to January 2017, approximately 18 months) | Progression-free survival is defined as the time from first dosing date to the date of the first documented tumor progression, as determined by the investigator according to RECIST 1.1 criteria, or death due to any cause, whichever occurs first. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. PFS was not assessed for this study due to the small number of participants. |
Countries
Finland, United States
Participant flow
Pre-assignment details
61 participants were enrolled; 41 participants entered the treatment period.
Participants by arm
| Arm | Count |
|---|---|
| PAC DL1 (DLT) Pancreatic Adenocarcinoma (PAC) Dose level 1, 400 mg ulocuplumab QW + 3 mg/kg nivolumab Q2W | 6 |
| PAC DL-1 (Tot) Pancreatic Adenocarcinoma (PAC) Dose level -1, 200 mg ulocuplumab QW + 3 mg/kg nivolumab Q2W | 27 |
| SCLC (Tot) All Small Cell Lung Cancer (SCLC) subjects in study, 1 subject received 400 mg ulocuplumab QW + 3 mg/kg nivolumab Q2W and 7 subjects received 200 mg ulocuplumab QW + 3 mg/kg nivolumab Q2W | 8 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Disease progression | 4 | 25 | 6 |
| Overall Study | Study drug toxicity | 2 | 0 | 2 |
| Overall Study | Subject request to discontinue treatment | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | PAC DL1 (DLT) | PAC DL-1 (Tot) | SCLC (Tot) | Total |
|---|---|---|---|---|
| Age, Continuous | 63.3 years STANDARD_DEVIATION 5.05 | 61.9 years STANDARD_DEVIATION 7.93 | 60.1 years STANDARD_DEVIATION 14.13 | 61.7 years STANDARD_DEVIATION 8.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 22 Participants | 7 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 25 Participants | 7 Participants | 38 Participants |
| Sex: Female, Male Female | 1 Participants | 14 Participants | 4 Participants | 19 Participants |
| Sex: Female, Male Male | 5 Participants | 13 Participants | 4 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 6 | 16 / 27 | 5 / 8 |
| other Total, other adverse events | 6 / 6 | 26 / 27 | 8 / 8 |
| serious Total, serious adverse events | 3 / 6 | 21 / 27 | 7 / 8 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs
The number participants who experienced on-study AEs, SAEs, and AEs requiring immune modulating medication is reported.
Time frame: From first dose until date of last dose of ulocuplumab or nivolumab plus 100 days (assessed up to January 2017, approximately 18 months)
Population: All treated participants. Participants in the SCLC (Tot) Arm were not evaluated for Immune-mediated AEs
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAC DL1 (DLT) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | Serious Adverse Events | 3 Participants |
| PAC DL1 (DLT) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | Adverse Events | 6 Participants |
| PAC DL1 (DLT) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | Immune-mediated AEs | 1 Participants |
| PAC DL-1 (Tot) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | Immune-mediated AEs | 3 Participants |
| PAC DL-1 (Tot) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | Adverse Events | 27 Participants |
| PAC DL-1 (Tot) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | Serious Adverse Events | 21 Participants |
| SCLC (Tot) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | Serious Adverse Events | 7 Participants |
| SCLC (Tot) | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Immune-mediated AEs | Adverse Events | 8 Participants |
Primary
Number of Participants With Electrocardiogram Abnormalities
The number of participants experiencing electrocardiogram abnormalities was reported for each arm
Time frame: From first dose to date of last dose plus 30 days
Population: Electrocardiogram data was not collected for any participants
Primary
Number of Participants With Laboratory Abnormalities
The number of participants who experienced on-study Grade 3 or 4 laboratory abnormalities (without Grade 3 or 4 abnormality at baseline) was reported for each arm.
Time frame: From first dose until date of last dose of ulocuplumab or nivolumab plus 100 days (assessed up to January 2017, approximately 18 months)
Population: All treated participants in PAC arms. Lab abnormality data was not collected for SCLC arm.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hyponatremia | 1 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Alkaline Phosphatase | 1 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Leukocytes | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Aspartate Aminotransferase | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Platelet Count | 1 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Bilirubin | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hemoglobin | 1 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hypokalemia | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Creatine | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Amylase | 1 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Alanine Aminotransferase | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Lipase | 1 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Hypernatremia | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Increased lymphocytes | 1 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Neutrophils | 0 Participants |
| PAC DL1 (DLT) | Number of Participants With Laboratory Abnormalities | Decreased platelet count | 1 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hypomagnesemia | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hemoglobin | 1 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Leukocytes | 1 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Neutrophils | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Platelet Count | 2 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Alanine Aminotransferase | 3 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Alkaline Phosphatase | 11 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Aspartate Aminotransferase | 5 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Bilirubin | 1 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Creatine | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hypernatremia | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hyponatremia | 3 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hypermagnesemia | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Decreased platelet count | 2 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hypercalcemia | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hypocalcemia | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hyperkalemia | 1 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Hypokalemia | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Amylase | 0 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Lipase | 1 Participants |
| PAC DL-1 (Tot) | Number of Participants With Laboratory Abnormalities | Increased lymphocytes | 2 Participants |
Primary
Objective Response Rate (ORR) Per RECIST 1.1 Criteria
ORR is defined as the number of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the number of treated participants. BOR is defined as the best response designation recorded between the first dose date and the date of progression per RECIST 1.1, or the date of subsequent anti-cancer therapy, whichever occurs first. CR= Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. PR= At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD)=At least a 20% increase in the sum of diameters of target lesions, referencing the smallest sum on study, and an absolute increase of at least 5 mm, or the appearance of one or more new lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, referencing the smallest sum diameters while on study.
Time frame: From first dose until disease progression or treatment discontinuation (assessed up to January 2017, approximately 18 months)
Population: All treated participants in PAC arms. ORR data was not collected for SCLC arm.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PAC DL1 (DLT) | Objective Response Rate (ORR) Per RECIST 1.1 Criteria | 0 Percentage of participants |
| PAC DL-1 (Tot) | Objective Response Rate (ORR) Per RECIST 1.1 Criteria | 0 Percentage of participants |
Primary
Overall Survival (OS)
If a Phase 2 comparative study is initiated and, for PAC only: Overall Survival is defined as the time from randomization to date of death due to any cause.
Time frame: From date of randomization to date of death (assessed up to study completion, approximately 18 months)
Population: OS data was not collected for any participants
Secondary
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from first dosing date to the date of the first documented tumor progression, as determined by the investigator according to RECIST 1.1 criteria, or death due to any cause, whichever occurs first. Participants who die without a reported prior progression will be considered to have progressed on the date of their death. PFS was not assessed for this study due to the small number of participants.
Time frame: From first dose to date of progression (assessed up to January 2017, approximately 18 months)
Population: PFS data was not collected for any participants