Advanced Cancer
Conditions
Brief summary
The purpose of this study is to determine whether BMS-986288 both by itself and in combination with Nivolumab is safe and tolerable in the treatment of select advanced solid tumors.
Interventions
DRUGBMS-986288
Specified dose on specified days
DRUGNivolumab
Specified dose on specified days
DRUGRegorafenib
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologic or cytologic confirmation of select solid tumor that is advanced (metastatic, recurrent, and/or unresectable) with measurable disease and have at least 1 lesion accessible for biopsy * Eastern Cooperative Oncology Group Performance Status of 0 or 1 * Received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to select solid tumor histologies
Exclusion criteria
* Active, known or suspected autoimmune disease * Active malignancy requiring concurrent intervention * Primary Central Nervous System (CNS) malignancies or tumors with CNS metastasis as the only site of disease, will be excluded Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Related Events for Cohorts 1A, 1B and 2B. | approximately 6 months | Safety releated events for Cohorts 1A, 1B and 2B. |
| Dose Limiting Toxicities Cohorts 1A, 1B and 2B. | approximately 5 weeks | A DLT is an adverse event or abnormal lab value not related to disease progression, illness, or other medications. The DLT evaluation period is 5 weeks (35 days) for both BMS-986288 monotherapy and combination dose escalation. Toxicities beyond this period will inform final dose decisions. Participants who discontinue due to a DLT or complete the 5-week period after receiving at least 2 doses are considered DLT-evaluable. Those who withdraw early or receive fewer than 2 doses for non-DLT reasons are not evaluable and may be replaced. Participants with dose delays for non-DLT reasons remain evaluable if they receive at least 2 doses within 8 weeks. |
| Objective Response Rate by BICR in Cohort 2C | approximately 2.15 Months | The percentage of all treated participants whose BOR is either CR or PR by BICR per RECIST v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC(0-T) for Cohorts 1A, 1B and 2B | On Cycle 1 Day 1 for Total and Intact, C4D1 for Intact | Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration. |
| AUC(Tau) for Cohorts 1A, 1B and 2B | On Cycle 1 Day 1 for Total and Intact, C4D1 for Intact | Area under the plasma concentration time-curve. AUC over the dosing interval. |
| Objective Response Rate in Cohorts 1A, 1B and 2B | approximately 2.15 Months | The percentage of all treated participants whose BOR is either CR or PR by Investigator per RECIST v1.1. |
| Duration of Response in Cohorts 1A, 1B and 2B | approximately 2.15 Months | Duration of response is defined as the time between the date of first documented response (CR or PR) that is subsequently confirmed, to the date of the 1st objectively documented tumor progression as determined by Investigator (per RECIST 1.1), or death due to any cause, whichever occurs first. |
| Time to Response in Cohorts 1A, 1B and 2B | approximately 2.15 Months | Time to response (TTR) assessed by investigator is defined as the time between the date of randomization and the first confirmed documented response (CR or PR) per RECIST 1.1 criteria. |
| Progression Free Survival in Cohorts 1A, 1B and 2B | approximately 2.15 Months | PFS is defined for all randomized participants as the date from randomization to the date of the documentation of disease progression by investigator or death due to any cause, whichever is earlier. |
| Duration of Response by BICR in Cohort 2C | approximately 2.5 Months | Duration of response is defined as the time between the date of first documented response (CR or PR) that is subsequently confirmed, to the date of the 1st objectively documented tumor progression as determined by BICR (per RECIST 1.1), or death due to any cause, whichever occurs first. |
| PFS by BICR in Cohort 2C | approximately 2.5 Months | PFS is defined for all randomized participants as the date from randomization to the date of the documentation of disease progression by BICR or death due to any cause, whichever is earlier. |
| Overall Survival in Cohort 2C | approximately 2.5 Months | OS is defined as the time from randomization to the time of death due to any cause. |
| Objective Response Rate by Investigator in Cohort 2C | approximately 2.5 Months | The percentage of all treated participants whose BOR is either CR or PR by Investigator per RECIST v1.1. |
| Duration of Response by Investigator in Cohort 2C | approximately 2.5 Months | Duration of response is defined as the time between the date of first documented response (CR or PR) that is subsequently confirmed, to the date of the 1st objectively documented tumor progression as determined by Investigator (per RECIST 1.1), or death due to any cause, whichever occurs first. |
| PFS by Investigator in Cohort 2C | approximately 2.5 Months | PFS is defined for all randomized participants as the date from randomization to the date of the documentation of disease progression by investigator or death due to any cause, whichever is earlier. |
| Safety Related Events in Cohort 2C | approximately 6 Months | Safety Related Events in Cohort 2C |
| C(Tau) for Cohorts 1A, 1B and 2B | On Cycle 1 Day 1 for Total and Intact, C4D1 for Intact | Ctau is defined as the concentration of study drug at the end of the dosing interval |
| Dose Limiting Toxicities in Cohort 2C | approximately 5 weeks | A DLT is an adverse event or abnormal lab value not related to disease progression, illness, or other medications. The DLT evaluation period is 5 weeks (35 days) for both BMS-986288 monotherapy and combination dose escalation. Toxicities beyond this period will inform final dose decisions. Participants who discontinue due to a DLT or complete the 5-week period after receiving at least 2 doses are considered DLT-evaluable. Those who withdraw early or receive fewer than 2 doses for non-DLT reasons are not evaluable and may be replaced. Participants with dose delays for non-DLT reasons remain evaluable if they receive at least 2 doses within 8 weeks. |
| Cmax for Cohorts 1A, 1B and 2B | On Cycle 1 Day 1 for Total and Intact, C4D1 for Intact | Cmax is defined as maximum plasma concentration of the drug. |
| Tmax for Cohorts 1A, 1B and 2B | On Cycle 1 Day 1 for Total and Intact, C4D1 for Intact | Tmax is defined is the time to maximum plasma concentration |
Countries
Argentina, Canada, Chile, France, Italy, Spain, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 61.3 Years STANDARD_DEVIATION 7.46 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 28 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 1 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 4 / 4 | 5 / 5 | 2 / 6 | 3 / 5 | 5 / 5 | 5 / 9 | 26 / 40 | 2 / 3 | 34 / 47 | 30 / 39 | 12 / 34 | 6 / 12 | 1 / 4 |
| other Total, other adverse events | 4 / 4 | 4 / 4 | 5 / 5 | 6 / 6 | 5 / 5 | 5 / 5 | 9 / 9 | 40 / 40 | 3 / 3 | 47 / 47 | 39 / 39 | 34 / 34 | 12 / 12 | 4 / 4 |
| serious Total, serious adverse events | 3 / 4 | 3 / 4 | 4 / 5 | 3 / 6 | 5 / 5 | 5 / 5 | 4 / 9 | 29 / 40 | 3 / 3 | 34 / 47 | 30 / 39 | 24 / 34 | 7 / 12 | 3 / 4 |
Outcome results
None listed