Cancer
Conditions
Brief summary
The purpose of this study is to investigate safety of experimental medication BMS-986242 and Nivolumab in patients with advanced cancers.
Interventions
DRUGBMS-986242
Specified dose on specified days
BIOLOGICALNivolumab
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Histologic or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease per RECIST v1.1 * Participants must have received and then progressed or been intolerant to at least 1 standard treatment regimen in the advanced or metastatic setting if such a therapy exists * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Ability to swallow tablets * Adequate bone marrow and organ function, as defined by the protocol
Exclusion criteria
* Participants with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease (patients with controlled brain metastasis allowed to enroll) * Ocular melanoma * Any significant acute or chronic medical illness * Prior malignancy * Other active malignancy requiring concurrent intervention * Prior organ allograft or allogeneic bone marrow transplantation * Participants with active, known, or suspected autoimmune disease * Requirement for daily supplemental oxygen * Uncontrolled or significant cardiovascular disease * Pre-existing liver disease * Gastrointestinal disease known to interfere with absorption Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AE) | From initiation of study treatment until 100 days after discontinuation of study treatment | The primary objective to establish safety to be measured by the primary endpoint of AEs |
| Number of Participants With Serious Adverse Events (SAE) | From the date of participant's written consent until 100 days after discontinuation of nivolumab or participation in the study | The primary objective to establish safety to be measured by the primary endpoint of SAEs |
| Number of Participants With Dose Limiting Toxicities (DLT) | Approximately 2 years | The primary objective to establish safety to be measured by the primary endpoint of dose limiting toxicities |
| Number of Participants With AEs Leading to Discontinuation | Approximately 2 years | The primary objective to establish safety to be measured by the primary endpoint of AEs leading to discontinuation |
| Number of Deaths | Approximately 2 years | The primary objective to establish safety to be measured by the primary endpoint of deaths |
| Number of Participants With Laboratory Abnormalities | Approximately 2 years | The primary objective to establish safety to be measured by the primary endpoint of clinical laboratory test abnormalities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Total Body Clearance (CLT/F) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Apparent Volume of Distribution at Steady State (Vss/F) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Accumulation Index (AI) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0. Accumulation index, calculated based on ratio of area under the curve (AUC) and Cmax at steady state to after the first dose. |
| Maximum Observed Plasma Concentration (Cmax) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Percent Urinary Recovery Over 72 Hours (%UR72) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Incidence of Anti-drug Antibody (ADA) to Nivolumab in Combination With BMS-986242 | Approximately 2 years | Baseline ADA-positive participant is defined as a participant who has a ADA detected sample at baseline. ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment. |
| Overall Response Rate (ORR) | Approximately 2 years | ORR in participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors |
| Percent Urinary Recovery Over 24 Hours (%UR24) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Time of Maximum Observed Plasma Concentration (Tmax) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Area Under the Concentration-time Curve From Time Zero to Infinity [AUC(INF)] | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Trough Observed Plasma Concentration at the End of the Dosing Interval (Ctrough) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
| Apparent Elimination Half-life (T-HALF) | Approximately 2 years | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 |
Countries
United States
Participant flow
Pre-assignment details
7 participants were enrolled and 5 of those participants entered treatment; reasons for 2 participants not entering treatment were due to: 1 death; 1 participant no longer met study criteria. Note: study terminated following starting dose of BMS-986242 12.5 mg; dosing did not escalate.
Participants by arm
| Arm | Count |
|---|---|
| BMS-986242 12.5 mg + Nivolumab 480 mg 2-week monotherapy of BMS986-242 (Cycle 0), followed by combination treatment cycles every 4 weeks for 104 weeks (or 26 cycles); each treatment cycle consists of daily oral dose of BMS-986242 and 1 dose of Nivolumab intravenously every 4 weeks on Day 1 of treatment cycle; every 2 treatment cycles decision may be made to add cycles of study treatment based on radiological tumor assessments | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Combination Therapy Period | Administrative reason by the Sponsor | 1 |
| Combination Therapy Period | Adverse Event unrelated to study drug | 1 |
| Combination Therapy Period | Disease progression | 2 |
| Combination Therapy Period | Study drug toxicity | 1 |
| Safety Follow-Up Period | Other reason | 2 |
| Safety Follow-Up Period | Participant withdrew consent | 1 |
Baseline characteristics
| Characteristic | BMS-986242 12.5 mg + Nivolumab 480 mg |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants |
| Age, Continuous | 67.8 Years STANDARD_DEVIATION 7.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Number of Deaths
The primary objective to establish safety to be measured by the primary endpoint of deaths
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986242 12.5 mg + Nivolumab 480 mg | Number of Deaths | NA Number of deaths |
Primary
Number of Participants With Adverse Events (AE)
The primary objective to establish safety to be measured by the primary endpoint of AEs
Time frame: From initiation of study treatment until 100 days after discontinuation of study treatment
Population: Study terminated, data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986242 12.5 mg + Nivolumab 480 mg | Number of Participants With Adverse Events (AE) | NA Number of participants |
Primary
Number of Participants With AEs Leading to Discontinuation
The primary objective to establish safety to be measured by the primary endpoint of AEs leading to discontinuation
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986242 12.5 mg + Nivolumab 480 mg | Number of Participants With AEs Leading to Discontinuation | NA Number of participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLT)
The primary objective to establish safety to be measured by the primary endpoint of dose limiting toxicities
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986242 12.5 mg + Nivolumab 480 mg | Number of Participants With Dose Limiting Toxicities (DLT) | NA Number of participants |
Primary
Number of Participants With Laboratory Abnormalities
The primary objective to establish safety to be measured by the primary endpoint of clinical laboratory test abnormalities
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986242 12.5 mg + Nivolumab 480 mg | Number of Participants With Laboratory Abnormalities | NA Number of participants |
Primary
Number of Participants With Serious Adverse Events (SAE)
The primary objective to establish safety to be measured by the primary endpoint of SAEs
Time frame: From the date of participant's written consent until 100 days after discontinuation of nivolumab or participation in the study
Population: Study terminated, data not reported due to privacy reasons
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986242 12.5 mg + Nivolumab 480 mg | Number of Participants With Serious Adverse Events (SAE) | NA Number of participants |
Secondary
Accumulation Index (AI)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0. Accumulation index, calculated based on ratio of area under the curve (AUC) and Cmax at steady state to after the first dose.
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Apparent Elimination Half-life (T-HALF)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Apparent Total Body Clearance (CLT/F)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Apparent Volume of Distribution at Steady State (Vss/F)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Area Under the Concentration-time Curve From Time Zero to Infinity [AUC(INF)]
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)]
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Incidence of Anti-drug Antibody (ADA) to Nivolumab in Combination With BMS-986242
Baseline ADA-positive participant is defined as a participant who has a ADA detected sample at baseline. ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment.
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Maximum Observed Plasma Concentration (Cmax)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Overall Response Rate (ORR)
ORR in participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Percent Urinary Recovery Over 24 Hours (%UR24)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Percent Urinary Recovery Over 72 Hours (%UR72)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Time of Maximum Observed Plasma Concentration (Tmax)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons
Secondary
Trough Observed Plasma Concentration at the End of the Dosing Interval (Ctrough)
The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0
Time frame: Approximately 2 years
Population: Study terminated, data not reported due to privacy reasons