BMS-986012 in Relapsed/Refractory SCLC

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

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 Overview

• Status: Completed
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Biological: Nivolumab; Biological: BMS-986012 (anti-fucosyl-GM1)

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St. Leonards, New South Wales, Australia, 2065
      • Local Institution - 0020
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Local Institution - 0011
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution - 0002
• Belgium
  • Gent, Belgium, 9000
    • Local Institution - 0015
  • Liege, Belgium, 4000
    • Local Institution - 0012
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0003
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Local Institution - 0017
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Local Institution - 0019
    • London, Ontario, Canada, N6A 4L6
      • Local Institution - 0010
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 0007
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Local Institution - 0008
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Local Institution - 0013
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Local Institution - 0009
• United States
  • New York
    • New York, New York, United States, 10065
      • Local Institution - 0004
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0001
    • Winston-Salem, North Carolina, United States, 27157
      • Local Institution - 0021

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation (Monotherapy) Dose -1; 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)
Experimental: Dose Escalation (Monotherapy) Dose 1; 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)
Experimental: Dose Escalation (Monotherapy) Dose 2; 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)
Experimental: Dose Escalation (Monotherapy) Dose 3; 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)
Experimental: Dose Escalation (Monotherapy) Dose 4; 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)
Experimental: 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	Biological: BMS-986012 (anti-fucosyl-GM1)
Experimental: 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	Biological: BMS-986012 (anti-fucosyl-GM1)
Experimental: 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	Biological: BMS-986012 (anti-fucosyl-GM1)
Experimental: 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	Biological: BMS-986012 (anti-fucosyl-GM1)
Experimental: 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	Biological: Nivolumab; Biological: BMS-986012 (anti-fucosyl-GM1)
Experimental: 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	Biological: Nivolumab; Biological: BMS-986012 (anti-fucosyl-GM1)
Experimental: 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	Biological: Nivolumab; Biological: BMS-986012 (anti-fucosyl-GM1)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events (AEs)	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.	From first dose to 100 days post last dose (Up to 64 months)
Number of Participants With Serious Adverse Events (SAEs)	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.	From first dose to 100 days post last dose (Up to 64 months)
Number of Participants With Adverse Events (AEs) Leading to Discontinuation	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.	From first dose to 100 days post last dose (Up to 64 months)
Number of Participants Who Died	Number of participants who died due to any cause.	From first dose to 100 days post last dose (Up to 64 months)
Number of Participants With Abnormal Hepatic Test	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	From first dose to 100 days post last dose (Up to 64 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BMS-986012 Maximum Observed Serum Concentration (Cmax)	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)	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 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T))	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 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU)	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 Observed Serum Concentration at the End of a Dosing Interval (Ctau)	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 Total Body Clearance (CLT)	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 Trough Observed Serum Concentration (Ctrough)	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 Average Concentration Over a Dosing Interval (Css-avg)	BMS-986012 Average concentration over a dosing interval ([AUC(TAU)/tau] (Css-avg).	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Accumulation Index (AI_AUC)	BMS-986012 accumulation index. Ratio of an exposure measure at steady state to that after the first dose.	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Cmax Accumulation Index (AI_Cmax)	BMS-986012 Cmax accumulation index (AI_Cmax). Ratio of an exposure measure at steady state to that after the first dose.	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Ctau Accumulation Index (AI_Ctau)	BMS-986012 Ctau accumulation index (AI_Ctau). Ratio of an exposure measure at steady state to that after the first dose.	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Effective Elimination (T-HALFeff)	BMS-986012 effective elimination (T-HALFeff) that explains the degree of accumulation observed for a specific exposure measure.	Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
Best Overall Response (BOR)	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	From first dose to the last tumor assessment prior to subsequent therapy (Up to 97 months)
Objective Response Rate (ORR)	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	From first dose date to the date of first documented disease progression (Up to 97 months)
Duration of Response (DoR)	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.	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)
Progression Free Survival (PFS)	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 mm	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)
Progression Free Survival Rate (PFSR)	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 mm	Weeks 12, 24, 36, 48, 60, 72
Number of Participants With Anti-BMS-986012 Antibodies (ADA)	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.	From first dose to 100 days following the last BMS-986012 dose (Up to 64 months)

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• FDA Safety Alerts and Recalls
• BMS Clinical Trial Patient Recruiting
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2014
• Primary Completion (Actual): December 21, 2022
• Study Completion (Actual): December 22, 2022

Study Registration Dates

• First Submitted: September 19, 2014
• First Submitted That Met QC Criteria: September 19, 2014
• First Posted (Estimated): September 25, 2014

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA001-030; 2014-002372-89 (EudraCT Number)