A Phase 1/2 Multicenter Study of BMS-986012 in Subjects With Relapsed/Refractory Small Cell Lung Cancer
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 106
- Locations
- 31
- Primary Endpoint
- Number of Participants With Adverse Events (AEs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Histological or cytological confirmed small cell lung cancer (SCLC)
- •Performance Status 0-1
- •Adequate organ function
- •Measurable disease
Exclusion Criteria
- •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
Arms & Interventions
Dose Escalation (Monotherapy) Dose 4
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Escalation (Monotherapy) Dose -1
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Escalation (Monotherapy) Dose 1
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Expansion (Monotherapy)- Cohort A (Refractory)
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Expansion (Monotherapy) Cohort B (Refractory)
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Escalation (Monotherapy) Dose 2
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Escalation (Monotherapy) Dose 3
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Expansion (Monotherapy) Cohort C (Sensitive)
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Expansion (Monotherapy) Cohort D (Sensitive)
BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Escalation (Combination) Dose 1
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
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Escalation (Combination) Dose 2
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
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Dose Expansion (Combination)- (Refractory and Sensitive)
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
Intervention: BMS-986012 (anti-fucosyl-GM1) (Biological)
Outcomes
Primary Outcomes
Number of Participants With Adverse Events (AEs)
Time Frame: 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
Time Frame: 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 Who Died
Time Frame: 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 Serious Adverse Events (SAEs)
Time Frame: 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 With Abnormal Hepatic Test
Time Frame: 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 Outcomes
- 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 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 Accumulation Index (AI_AUC)(Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post 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))
- 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 Average Concentration Over a Dosing Interval (Css-avg)(Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose))
- Objective Response Rate (ORR)(From first dose date to the date of first documented disease progression (Up to 97 months))
- Progression Free Survival Rate (PFSR)(Weeks 12, 24, 36, 48, 60, 72)
- BMS-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 Effective Elimination (T-HALFeff)(Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose))
- 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))
- BMS-986012 Cmax Accumulation Index (AI_Cmax)(Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose))
- BMS-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 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))
- Best Overall Response (BOR)(From first dose to the last tumor assessment prior to subsequent therapy (Up to 97 months))
- 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))
- 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))
- BMS-986012 Ctau Accumulation Index (AI_Ctau)(Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose))