Advanced Solid Tumors, Advanced B-cell NHL
Conditions
Brief summary
The purpose of this study is to determine which doses of Urelumab and Nivolumab are safe and tolerable when they are given together.
Interventions
BIOLOGICALUrelumab
BIOLOGICALNivolumab
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: * For Dose Escalation: * Subjects with any previously treated advanced (metastatic or refractory) solid tumor type and B-cell non-Hodgkin lymphoma * For Cohort Expansion: * Subjects must have a previously treated advanced solid tumor or B cell non-Hodgkin's lymphoma to be eligible * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * For certain subjects, willing and able to provide pre-treatment and on-treatment fresh tumor biopsy * Women of child-bearing potential and men must use an acceptable method of contraception during treatment and for 23 weeks after treatment for women and 31 weeks for men
Exclusion criteria
* Known central nervous system metastases or central nervous system as the only source of disease * Other concomitant malignancies (with some exceptions per protocol) * Active, known or suspected autoimmune disease * Uncontrolled or significant cardiovascular disease * History of hepatitis (B or C) * History of active or latent tuberculosis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Incidence of Adverse Events. | From day 1 until 100 days after participant last dose of study drug. |
| The Incidence of Seriuos Adverse Events. | From day 1 until 100 days after participant last dose of the study drug. |
| The Incidence of Death. | From day 1 until 100 days after participant last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years | DOR is defined as the number of days between the date of first response and the subsequent date of objectively documented disease progression based on the criteria (RECIST v1.1) or relapse based on IWG, or death due to any cause, if death occurred within 100 days after last dose, whichever occurs first. Data was not collected due to discontinuation of the study/Due to study termination. |
| Progression-free Survival Rate (PFSR) | Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years. | PFSR is defined as the probability of a subject remaining progression-free and surviving a specific length of time. Data was not collected due to discontinuation of the study/Due to study termination. |
| Maximum Observed Serum Concentration (Cmax) | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | Data was not collected due to discontinuation of the study/Due to study termination. |
| Time of Maximum Observed Serum Concentration (Tmax) | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | Data was not collected due to discontinuation of the study/Due to study termination. |
| Best Overall Response (BOR) | Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years. | The total number of subjects whose best overall response (BOR) is either a complete response or partial response for solid tumors and complete remission or partial remission for B-cell NHL, divided by the total number of subjects in the population of interest. |
| Trough Observed Plasma Concentration(Ctrough) | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | Data was not collected due to discontinuation of the study/Due to study termination. |
| End of Infusion Concentration (Ceoinf) | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | Data was not collected due to discontinuation of the study/Due to study termination. |
| Area Under the Plasma Concentration-time Curve, 0 to Time of Last Quantifiable Concentration (AUC(0-T) | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | Data was not collected due to discontinuation of the study/Due to study termination. |
| Area Under the Concentration-time Curve in One Dosing Interval (AUCTAU) | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days | Data was not collected due to discontinuation of the study/Due to study termination. |
| Objective Response Rate (ORR) | Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years. | Objective response rate (ORR) is defined as the total number of subjects whose BOR is either CR or PR divided by the total number of subjects in the population of interest. |
| Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab | Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days. | — |
Countries
France, Germany, Spain, United States
Participant flow
Pre-assignment details
160 enrolled and treated
Participants by arm
| Arm | Count |
|---|---|
| TRT A URE3 Q4WK+NIV3 Q2WK | 6 |
| TRT B URE8 Q4WK+NIV3 Q2WK | 4 |
| TRT D URE8 Q4WK+NIV240mg Q2WK | 150 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 8 |
| Overall Study | Completed treatment as per protocol | 0 | 1 | 22 |
| Overall Study | Death | 0 | 0 | 1 |
| Overall Study | Disease progression | 4 | 3 | 98 |
| Overall Study | Other | 0 | 0 | 1 |
| Overall Study | Study drug toxicity | 1 | 0 | 10 |
| Overall Study | Subject discontinued study drug | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 |
Baseline characteristics
| Characteristic | TRT A | TRT B | TRT D | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 2 Participants | 83 Participants | 90 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 2 Participants | 67 Participants | 70 Participants |
| Age, Continuous | 64.7 Years STANDARD_DEVIATION 9.4 | 64.0 Years STANDARD_DEVIATION 8.52 | 63.8 Years STANDARD_DEVIATION 11.71 | 63.9 Years STANDARD_DEVIATION 11.52 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 2 Participants | 107 Participants | 114 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 42 Participants | 44 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 9 Participants | 9 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 | 4 Participants | 4 Participants |
| Race (NIH/OMB) White | 6 Participants | 4 Participants | 136 Participants | 146 Participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 47 Participants | 51 Participants |
| Sex: Female, Male Male | 4 Participants | 2 Participants | 103 Participants | 109 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 6 | 2 / 4 | 93 / 150 |
| other Total, other adverse events | 6 / 6 | 4 / 4 | 147 / 150 |
| serious Total, serious adverse events | 3 / 6 | 3 / 4 | 86 / 150 |
Outcome results
Primary
The Incidence of Adverse Events.
Time frame: From day 1 until 100 days after participant last dose of study drug.
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TRT A | The Incidence of Adverse Events. | 6 Number of participants |
| TRT B | The Incidence of Adverse Events. | 4 Number of participants |
| TRT D | The Incidence of Adverse Events. | 150 Number of participants |
Primary
The Incidence of Death.
Time frame: From day 1 until 100 days after participant last dose of study drug.
Population: All Treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TRT A | The Incidence of Death. | 6 Number of participants |
| TRT B | The Incidence of Death. | 2 Number of participants |
| TRT D | The Incidence of Death. | 93 Number of participants |
Primary
The Incidence of Seriuos Adverse Events.
Time frame: From day 1 until 100 days after participant last dose of the study drug.
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TRT A | The Incidence of Seriuos Adverse Events. | 3 Number of participants |
| TRT B | The Incidence of Seriuos Adverse Events. | 3 Number of participants |
| TRT D | The Incidence of Seriuos Adverse Events. | 86 Number of participants |
Secondary
Area Under the Concentration-time Curve in One Dosing Interval (AUCTAU)
Data was not collected due to discontinuation of the study/Due to study termination.
Time frame: Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days
Population: Data was not collected due to discontinuation of the study/Due to study termination.
Secondary
Area Under the Plasma Concentration-time Curve, 0 to Time of Last Quantifiable Concentration (AUC(0-T)
Data was not collected due to discontinuation of the study/Due to study termination.
Time frame: Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.
Population: Data was not collected due to discontinuation of the study/Due to study termination.
Secondary
Best Overall Response (BOR)
The total number of subjects whose best overall response (BOR) is either a complete response or partial response for solid tumors and complete remission or partial remission for B-cell NHL, divided by the total number of subjects in the population of interest.
Time frame: Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.
Population: All treated Participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TRT A | Best Overall Response (BOR) | Complete response | 0 Number of participants |
| TRT A | Best Overall Response (BOR) | Partial response | 1 Number of participants |
| TRT B | Best Overall Response (BOR) | Complete response | 0 Number of participants |
| TRT B | Best Overall Response (BOR) | Partial response | 1 Number of participants |
| TRT D | Best Overall Response (BOR) | Partial response | 2 Number of participants |
| TRT D | Best Overall Response (BOR) | Complete response | 0 Number of participants |
| TRT A - Melanoma pd1/Pd-l1 Naive | Best Overall Response (BOR) | Partial response | 1 Number of participants |
| TRT A - Melanoma pd1/Pd-l1 Naive | Best Overall Response (BOR) | Complete response | 0 Number of participants |
| TRT B - | Best Overall Response (BOR) | Complete response | 1 Number of participants |
| TRT B - | Best Overall Response (BOR) | Partial response | 0 Number of participants |
| TRT D - Melanoma pd1/Pd-l1 Naive | Best Overall Response (BOR) | Complete response | 6 Number of participants |
| TRT D - Melanoma pd1/Pd-l1 Naive | Best Overall Response (BOR) | Partial response | 15 Number of participants |
| TRT A - SCCHN | Best Overall Response (BOR) | Partial response | 0 Number of participants |
| TRT A - SCCHN | Best Overall Response (BOR) | Complete response | 0 Number of participants |
| TRT D - SCCHN | Best Overall Response (BOR) | Complete response | 1 Number of participants |
| TRT D - SCCHN | Best Overall Response (BOR) | Partial response | 0 Number of participants |
| TRT A - Other Solid Tumors | Best Overall Response (BOR) | Partial response | 0 Number of participants |
| TRT A - Other Solid Tumors | Best Overall Response (BOR) | Complete response | 0 Number of participants |
| TRT B - Other Solid Tumors | Best Overall Response (BOR) | Complete response | 0 Number of participants |
| TRT B - Other Solid Tumors | Best Overall Response (BOR) | Partial response | 0 Number of participants |
| TRT D - DLBCL | Best Overall Response (BOR) | Complete response | 0 Number of participants |
| TRT D - DLBCL | Best Overall Response (BOR) | Partial response | 0 Number of participants |
| TRT D - FL | Best Overall Response (BOR) | Partial response | 0 Number of participants |
| TRT D - FL | Best Overall Response (BOR) | Complete response | 0 Number of participants |
Secondary
Duration of Response (DOR)
DOR is defined as the number of days between the date of first response and the subsequent date of objectively documented disease progression based on the criteria (RECIST v1.1) or relapse based on IWG, or death due to any cause, if death occurred within 100 days after last dose, whichever occurs first. Data was not collected due to discontinuation of the study/Due to study termination.
Time frame: Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years
Population: Data was not collected due to discontinuation of the study/Due to study termination.
Secondary
End of Infusion Concentration (Ceoinf)
Data was not collected due to discontinuation of the study/Due to study termination.
Time frame: Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.
Population: Data was not collected due to discontinuation of the study/Due to study termination.
Secondary
Maximum Observed Serum Concentration (Cmax)
Data was not collected due to discontinuation of the study/Due to study termination.
Time frame: Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.
Population: Data was not collected due to discontinuation of the study/Due to study termination.
Secondary
Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the total number of subjects whose BOR is either CR or PR divided by the total number of subjects in the population of interest.
Time frame: Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.
Population: All treated Participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| TRT A | Objective Response Rate (ORR) | 5.0 Percentage of participants |
| TRT B | Objective Response Rate (ORR) | 5.0 Percentage of participants |
| TRT D | Objective Response Rate (ORR) | 10.0 Percentage of participants |
| TRT A - Melanoma pd1/Pd-l1 Naive | Objective Response Rate (ORR) | 25.0 Percentage of participants |
| TRT B - | Objective Response Rate (ORR) | 100.0 Percentage of participants |
| TRT D - Melanoma pd1/Pd-l1 Naive | Objective Response Rate (ORR) | 48.8 Percentage of participants |
| TRT A - SCCHN | Objective Response Rate (ORR) | 0 Percentage of participants |
| TRT D - SCCHN | Objective Response Rate (ORR) | 4.8 Percentage of participants |
| TRT A - Other Solid Tumors | Objective Response Rate (ORR) | 0 Percentage of participants |
| TRT B - Other Solid Tumors | Objective Response Rate (ORR) | 0 Percentage of participants |
| TRT D - DLBCL | Objective Response Rate (ORR) | 0 Percentage of participants |
| TRT D - FL | Objective Response Rate (ORR) | 0 Percentage of participants |
Secondary
Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab
Time frame: Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TRT A | Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab | Baseline ADA positive | 5 Number of participants |
| TRT A | Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab | ADA positive | 55 Number of participants |
| TRT A | Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab | ADA negative | 78 Number of participants |
| TRT B | Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab | Baseline ADA positive | 2 Number of participants |
| TRT B | Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab | ADA positive | 9 Number of participants |
| TRT B | Occurrence of Specific Anti-drug Antibodies (ADA) to Urelumab and Nivolumab | ADA negative | 119 Number of participants |
Secondary
Progression-free Survival Rate (PFSR)
PFSR is defined as the probability of a subject remaining progression-free and surviving a specific length of time. Data was not collected due to discontinuation of the study/Due to study termination.
Time frame: Every 8 weeks for Cycle 1 through Cycle 6 then every 12 weeks thereafter for approximately 2 years.
Population: Data was not collected due to discontinuation of the study/Due to study termination.
Secondary
Time of Maximum Observed Serum Concentration (Tmax)
Data was not collected due to discontinuation of the study/Due to study termination.
Time frame: Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.
Population: Data was not collected due to discontinuation of the study/Due to study termination.
Secondary
Trough Observed Plasma Concentration(Ctrough)
Data was not collected due to discontinuation of the study/Due to study termination.
Time frame: Cycles 1, 2, 3, 4, 6, and followup Days up to 100 days.
Population: Data was not collected due to discontinuation of the study/Due to study termination.