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BMS-986012 in Relapsed/Refractory SCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02247349
Recruitment Status : Active, not recruiting
First Posted : September 25, 2014
Last Update Posted : January 31, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Small Cell Lung Cancer Biological: BMS-986012 (anti-fucosyl-GM1) Biological: Nivolumab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 172 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Multicenter Study of BMS-986012 in Subjects With Relapsed/Refractory Small Cell Lung Cancer
Actual Study Start Date : October 30, 2014
Estimated Primary Completion Date : October 23, 2019
Estimated Study Completion Date : October 24, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Nivolumab

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: BMS-986012 (anti-fucosyl-GM1)
Biological: Nivolumab
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: BMS-986012 (anti-fucosyl-GM1)
Biological: Nivolumab
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: BMS-986012 (anti-fucosyl-GM1)
Biological: Nivolumab



Primary Outcome Measures :
  1. 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 [ Time Frame: 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) ]
    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


Secondary Outcome Measures :
  1. Maximum observed serum concentration (Cmax) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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) ]
  2. Maximum observed serum concentration (Cmax) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab [ Time Frame: 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) ]
  3. Time of maximum observed serum concentration (Tmax) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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) ]
  4. Time of maximum observed serum concentration (Tmax) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab [ Time Frame: 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) ]
  5. Observed serum concentration at the end of a dosing interval (Ctau) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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) ]
  6. Observed serum concentration at the end of a dosing interval (Ctau) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab [ Time Frame: 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) ]
  7. 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 [ Time Frame: 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) ]
  8. Area under the serum concentration-time curve from time zero to time t (AUC(0-t)) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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) ]
  9. Area under the serum concentration-time curve in one dosing interval (AUC(TAU)) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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) ]
  10. Area under the serum concentration-time curve in one dosing interval (AUC(TAU)) for BMS-986012 (anti-fucosyl-GM1) in combination with Nivolumab [ Time Frame: 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) ]
  11. Best overall response (BOR) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: Approximately every 6 weeks until disease progression or every 3-4 months for subjects with a confirmed response (Approx duration of study 3 years) ]
    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

  12. Objective Response Rate (ORR) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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): 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

  13. Duration of Response for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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: defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first

  14. Progression Free Survival (PFS) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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): 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

  15. Progression Free Survival Rate (PFSR) at week "t"; for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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": defined as the proportion of subjects who remain progression free and surviving at "t" weeks (t=12, 24, 36, etc)

  16. Overall Survival (OS) for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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): 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

  17. Overall Survival Rate (OSR) at month "t" for BMS-986012 (anti-fucosyl-GM1) [ Time Frame: 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": defined as the proportion of subjects surviving at "t" months (eg, t=6, 12, 24 months, etc)

  18. 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 [ Time Frame: 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) ]
  19. 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 [ Time Frame: 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) ]
  20. 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 [ Time Frame: At multiple timepoints during first cycle, then Day 1 of subsequent cycles and at end of treatment (Approx duration of study 3 years) ]
  21. 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 [ Time Frame: At multiple timepoints during first cycle, then Day 1 of subsequent cycles and at end of treatment (Approx duration of study 3 years) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02247349


Locations
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United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Wake Forest Baptist Health
Winston-Salem, North Carolina, United States, 27157
Australia, New South Wales
Local Institution
St. Leonards, New South Wales, Australia, 2065
Australia, Queensland
Local Institution
Brisbane, Queensland, Australia, 4102
Australia, Victoria
Local Institution
Clayton, Victoria, Australia, 3168
Belgium
Uz Gent
Gent, Belgium, 9000
Local Institution
Liege, Belgium, 4000
Canada, Alberta
Cross Cancer Institute
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Nova Scotia
Nova Scotia Health Authority QEII Health Sciences Centre
Halifax, Nova Scotia, Canada, B3H 2Y9
Canada, Ontario
Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program
London, Ontario, Canada, N6A 4L6
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Korea, Republic of
Local Institution
Seoul, Korea, Republic of, 03080
Netherlands
Radboud Universitair Medisch Centrum
Nijmegen, Netherlands, 6525 GA
Puerto Rico
Local Institution
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb

Additional Information:
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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02247349     History of Changes
Other Study ID Numbers: CA001-030
2014-002372-89 ( EudraCT Number )
First Posted: September 25, 2014    Key Record Dates
Last Update Posted: January 31, 2019
Last Verified: January 2019
Additional relevant MeSH terms:
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Lung Neoplasms
Small Cell Lung Carcinoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Nivolumab
Antineoplastic Agents, Immunological
Antineoplastic Agents