BMS-986012 in Relapsed/Refractory SCLC

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1/2 Multicenter Study of BMS-986012 in Subjects With Relapsed/Refractory Small Cell Lung Cancer

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Biological: BMS-986012 (anti-fucosyl-GM1)
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation (Monotherapy) Dose -1<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Escalation (Monotherapy) Dose 1<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Escalation (Monotherapy) Dose 2<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Escalation (Monotherapy) Dose 3<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Escalation (Monotherapy) Dose 4<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Expansion (Monotherapy)- Cohort A (Refractory)<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Expansion (Monotherapy) Cohort B (Refractory)<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Expansion (Monotherapy) Cohort C (Sensitive)<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Expansion (Monotherapy) Cohort D (Sensitive)<br>BMS-986012 (anti-fucosyl-GM1) Intravenous solution once every 3 weeks until disease progression/clinical deterioration or unacceptable toxicity | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> |
| Experimental: Dose Escalation (Combination) Dose 1<br>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 | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> Biological: Nivolumab<br> <br> |
| Experimental: Dose Escalation (Combination) Dose 2<br>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 | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> Biological: Nivolumab<br> <br> |
| Experimental: Dose Expansion (Combination)- (Refractory and Sensitive)<br>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 | Biological: BMS-986012 (anti-fucosyl-GM1)<br> <br> Biological: Nivolumab<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as measured by frequency of worst grade of adverse events (AEs), worst grade of serious adverse events (SAEs), incidence of adverse events leading to discontinuations, and deaths | Safety as measured by frequency of worst grade of adverse events (AEs), worst grade of serious adverse events (SAEs), incidence of adverse events leading to discontinuations, and deaths graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), as appropriate | Weekly for 1st and 2nd 21-day cycles, then once every 3 weeks during study treatment, at end of treatment and every 30 days during clinical follow-up until resolution of adverse events or 100 days after the last dose of study medication (Approx 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed serum concentration (Cmax) for BMS-986012 (anti-fucosyl-GM1) |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Maximum observed serum concentration (Cmax) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Time of maximum observed serum concentration (Tmax) for BMS-986012 (anti-fucosyl-GM1) |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Time of maximum observed serum concentration (Tmax) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Observed serum concentration at the end of a dosing interval (Ctau) for BMS-986012 (anti-fucosyl-GM1) |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Observed serum concentration at the end of a dosing interval (Ctau) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Area under the serum concentration-time curve from time zero to time t (AUC(0-t)) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Area under the serum concentration-time curve from time zero to time t (AUC(0-t)) for BMS-986012 (anti-fucosyl-GM1) |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Area under the serum concentration-time curve in one dosing interval (AUC(TAU)) for BMS-986012 (anti-fucosyl-GM1) |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Area under the serum concentration-time curve in one dosing interval (AUC(TAU)) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab |  | At multiple timepoints during first 4 cycles then every 4th cycle, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Best overall response (BOR) for BMS-986012 (anti-fucosyl-GM1) | Best overall response (BOR): defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy | Approximately every 6 weeks until disease progression or every 3-4 months for subjects with a confirmed response (Approx duration of study 3 years) | 
| Objective Response Rate (ORR) for BMS-986012 (anti-fucosyl-GM1) | Objective Response Rate (ORR): defined as the total number of subjects whose best overall response (BOR) is either a complete response (CR) or partial response (PR) divided by the total number of subjects in the population of interest | Approximately every 6 weeks until disease progression or every 3-4 months for subjects with a confirmed response (Approx duration of study 3 years) | 
| Duration of Response for BMS-986012 (anti-fucosyl-GM1) | Duration of Response: defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first | Approximately every 6 weeks until disease progression or every 3-4 months for subjects with a confirmed response (Approx duration of study 3 years) | 
| Progression Free Survival (PFS) for BMS-986012 (anti-fucosyl-GM1) | Progression Free Survival (PFS): defined as the time from the first dose of study medication to the date of the first objective documentation of tumor progression or death due to any cause | Approximately every 6 weeks until disease progression or every 3-4 months for subjects with a confirmed response (Approx duration of study 3 years) | 
| Progression Free Survival Rate (PFSR) at week t; for BMS-986012 (anti-fucosyl-GM1) | Progression Free Survival Rate (PFSR) at week t: defined as the proportion of subjects who remain progression free and surviving at t weeks (t=12, 24, 36, etc) | Approximately every 6 weeks until disease progression or every 3-4 months for subjects with a confirmed response (Approx duration of study 3 years) | 
| Overall Survival (OS) for BMS-986012 (anti-fucosyl-GM1) | Overall Survival (OS): defined as the time between the date of first dose of study medication and the date of death. For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive | Approximately every 6 weeks until disease progression or every 3-4 months for subjects with a confirmed response (Approx duration of study 3 years) | 
| Overall Survival Rate (OSR) at month t for BMS-986012 (anti-fucosyl-GM1) | Overall Survival Rate (OSR) at month t: defined as the proportion of subjects surviving at t months (eg, t=6, 12, 24 months, etc) | Approximately every 6 weeks until disease progression or every 3-4 months for subjects with a confirmed response (Approx duration of study 3 years) | 
| Occurrence of specific anti-drug antibodies (ADA) to BMS-986012 every 3 weeks for first 3 cycles then every 4 cycles, at end of treatment and during clinical follow-up |  | Every 3 weeks for first 3 cycles then every 4 cycles, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Occurrence of specific anti-drug antibodies (ADA) to BMS-986012 in combination with Nivolumab every 3 weeks for first 3 cycles then every 4 cycles, at end of treatment and during clinical follow-up |  | Every 3 weeks for first 3 cycles then every 4 cycles, at end of treatment and during clinical follow-up (Approx duration of study 3 years) | 
| Changes in the QTcF following administration of BMS-986012 at multiple timepoints during first cycle, then Day 1 of subsequent cycles and at end of treatment |  | At multiple timepoints during first cycle, then Day 1 of subsequent cycles and at end of treatment (Approx duration of study 3 years) | 
| Changes in the QTcF following administration of BMS-986012 in combination with Nivolumab at multiple timepoints during first cycle, then Day 1 of subsequent cycles and at end of treatment |  | At multiple timepoints during first cycle, then Day 1 of subsequent cycles and at end of treatment (Approx duration of study 3 years) |