BMS-986012 in Relapsed/Refractory SCLC
- Conditions
- Small Cell Lung Cancer
- Interventions
- Biological: BMS-986012 (anti-fucosyl-GM1)Biological: Nivolumab
- Registration Number
- NCT02247349
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to determine the safety, tolerability, pharmacokinetics, immunogenicity, antitumor activity and pharmacodynamics of BMS-986012 alone and in combination with nivolumab in patients with relapsed/refractory SCLC.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 106
- Histological or cytological confirmed small cell lung cancer (SCLC)
- Performance Status 0-1
- Adequate organ function
- Measurable disease
- Known or suspected brain metastasis
- Small cell cancer not lung in origin
- Significant or acute medical illness
- Uncontrolled or significant cardiac disease
- Infection
- ≥ Grade 2 peripheral neuropathy
- Concomitant malignancies
- HIV related disease or known or suspected HIV+
- Hepatitis B or C infection
- ECG abnormalities as defined by the protocol
- Allergies or hypersensitivities to monoclonal antibodies, BMS-986012 or related compounds, including fucosyl-GM1 vaccine and Nivolumab
Other protocol defined inclusion/exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Dose Expansion (Monotherapy) Cohort B (Refractory) BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Escalation (Combination) Dose 2 BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity in combination with Nivolumab specified dose on specified days Dose Escalation (Monotherapy) Dose 4 BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Escalation (Monotherapy) Dose 1 BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Escalation (Monotherapy) Dose 2 BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Expansion (Monotherapy) Cohort D (Sensitive) BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Expansion (Monotherapy)- Cohort A (Refractory) BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Expansion (Monotherapy) Cohort C (Sensitive) BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Escalation (Combination) Dose 1 BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity in combination with Nivolumab specified dose on specified days Dose Escalation (Combination) Dose 1 Nivolumab BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity in combination with Nivolumab specified dose on specified days Dose Escalation (Monotherapy) Dose -1 BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Escalation (Monotherapy) Dose 3 BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity Dose Escalation (Combination) Dose 2 Nivolumab BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity in combination with Nivolumab specified dose on specified days Dose Expansion (Combination)- (Refractory and Sensitive) BMS-986012 (anti-fucosyl-GM1) BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity in combination with Nivolumab specified dose on specified days Dose Expansion (Combination)- (Refractory and Sensitive) Nivolumab BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity in combination with Nivolumab specified dose on specified days
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) From first dose to 100 days post last dose (Up to 64 months) Number of participants with any grade adverse events (AEs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Number of Participants With Adverse Events (AEs) Leading to Discontinuation From first dose to 100 days post last dose (Up to 64 months) Number of participants with any grade adverse events (AEs) leading to discontinuation. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Number of Participants With Serious Adverse Events (SAEs) From first dose to 100 days post last dose (Up to 64 months) Number of participants with any grade serious adverse events (SAEs). A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose:
* results in death
* is life-threatening
* requires inpatient hospitalization or causes prolongation of existing hospitalization
* results in persistent or significant disability/incapacity
* is a congenital anomaly/birth defect
* is an important medical event Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.Number of Participants Who Died From first dose to 100 days post last dose (Up to 64 months) Number of participants who died due to any cause.
Number of Participants With Abnormal Hepatic Test From first dose to 100 days post last dose (Up to 64 months) Number of participants with laboratory abnormalities in specific hepatic tests. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized:
* ALT or AST \> 5xULN, \> 3xULN, and \> 2xULN
* Any of ALT, AST, Total Bilirubin or ALP \> 8xULN
* Total bilirubin \> 3xULN
ALT = Alanine Aminotransferase; AST = Aspartate Aminotransferase; ULN = Upper Limit of Normal
- Secondary Outcome Measures
Name Time Method BMS-986012 Maximum Observed Serum Concentration (Cmax) Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose) BMS-986012 maximum observed serum concentration (Cmax).
BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) BMS-986012 time of maximum observed serum concentration (Tmax).
BMS-986012 Accumulation Index (AI_AUC) Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) BMS-986012 accumulation index. Ratio of an exposure measure at steady state to that after the first dose.
Number of Participants With Anti-BMS-986012 Antibodies (ADA) From first dose to 100 days following the last BMS-986012 dose (Up to 64 months) Number of participants with anti-BMS-986012 antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is a participant with baseline ADA positive sample (Day 1 predose). ADA-positive participant is a participant with at least one ADA positive sample relative to baseline at any time after initiation of treatment during the defined observation time period. ADA negative participant is a participant with no ADA positive sample after the initiation of treatment.
BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose) BMS-986012 area under the serum concentration-time curve in one dosing interval AUC (TAU).
BMS-986012 Average Concentration Over a Dosing Interval (Css-avg) Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) BMS-986012 Average concentration over a dosing interval (\[AUC(TAU)/tau\] (Css-avg).
Objective Response Rate (ORR) From first dose date to the date of first documented disease progression (Up to 97 months) ORR is defined as the percent of participants whose BOR is either CR or PR. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm
Progression Free Survival Rate (PFSR) Weeks 12, 24, 36, 48, 60, 72 PFSR is defined as the percent of participants who remain progression free and surviving at "t" weeks (t= 12, 24, 36, 48, 60, 72).
Progressive Disease (PD)=At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mmBMS-986012 Total Body Clearance (CLT) Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose) BMS-986012 total body clearance (CLT).
BMS-986012 Effective Elimination (T-HALFeff) Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) BMS-986012 effective elimination (T-HALFeff) that explains the degree of accumulation observed for a specific exposure measure.
Progression Free Survival (PFS) From first dose to the date of first documented disease progression or death due to any cause, if death occurred within 100 days after last BMS-986012 dose (Up to 97 months) PFS is defined as the time from the date of first dose of study medication to the date of the first objective documentation of tumor progression or death due to any cause, if death occurred within 100 days after last BMS-986012 dose.
Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mmBMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose) BMS-986012 area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC (0-T)).
BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose) BMS-986012 observed serum concentration at the end of a dosing interval (Ctau).
BMS-986012 Cmax Accumulation Index (AI_Cmax) Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) BMS-986012 Cmax accumulation index (AI_Cmax). Ratio of an exposure measure at steady state to that after the first dose.
Best Overall Response (BOR) From first dose to the last tumor assessment prior to subsequent therapy (Up to 97 months) BOR defined as the best response designation over the study as a whole. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = At least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm
BMS-986012 Trough Observed Serum Concentration (Ctrough) Cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, cycle 7 day 1, cycle 11 day 1. cycle 15 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose) BMS-986012 trough observed serum concentration (Ctrough).
BMS-986012 Ctau Accumulation Index (AI_Ctau) Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) BMS-986012 Ctau accumulation index (AI_Ctau). Ratio of an exposure measure at steady state to that after the first dose.
Duration of Response (DoR) From the date of first dose to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 97 months) DoR is defined as the time from first response (CR or PR) to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who remain alive and have not progressed will be censored on the date of their last tumor assessment.
Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR )= At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm
Median DOR will only be evaluated provided there are enough responding participants to warrant inclusion.
Trial Locations
- Locations (16)
Local Institution - 0015
🇧🇪Gent, Belgium
Local Institution - 0012
🇧🇪Liege, Belgium
Local Institution - 0009
🇵🇷San Juan, Puerto Rico
Local Institution - 0003
🇨🇦Edmonton, Alberta, Canada
Local Institution - 0008
🇰🇷Seoul, Korea, Republic of
Local Institution - 0017
🇨🇦Halifax, Nova Scotia, Canada
Local Institution - 0011
🇦🇺Brisbane, Queensland, Australia
Local Institution - 0007
🇨🇦Toronto, Ontario, Canada
Local Institution - 0002
🇦🇺Clayton, Victoria, Australia
Local Institution - 0019
🇨🇦Hamilton, Ontario, Canada
Local Institution - 0020
🇦🇺St. Leonards, New South Wales, Australia
Local Institution - 0010
🇨🇦London, Ontario, Canada
Local Institution - 0013
🇳🇱Nijmegen, Netherlands
Local Institution - 0004
🇺🇸New York, New York, United States
Local Institution - 0001
🇺🇸Durham, North Carolina, United States
Local Institution - 0021
🇺🇸Winston-Salem, North Carolina, United States