BMS-986012 in Relapsed/Refractory SCLC

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02247349
• Collaborator: (none)
• Enrollment: 107
• Locations: 16
• Arms: 12
• Anticipated Duration (Months): 91.3
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 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: Nov 14, 2014
• Anticipated Primary Completion Date: Jun 23, 2022
• Anticipated Study Completion Date: Jun 24, 2022

Arms and Interventions

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

Outcome Measures

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 [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) [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 [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) [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 [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) [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 [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 [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) [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) [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 [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) [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) [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) [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) [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) [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) [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) [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 [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 [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 [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 [At multiple timepoints during first cycle, then Day 1 of subsequent cycles and at end of treatment (Approx duration of study 3 years)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering Nassau	New York	New York	United States	10065
2	Duke University Medical Center	Durham	North Carolina	United States	27710
3	Wake Forest Baptist Health	Winston-Salem	North Carolina	United States	27157
4	Local Institution	St. Leonards	New South Wales	Australia	2065
5	Local Institution	Brisbane	Queensland	Australia	4102
6	Local Institution	Clayton	Victoria	Australia	3168
7	Uz Gent	Gent		Belgium	9000
8	Local Institution	Liege		Belgium	4000
9	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
10	Nova Scotia Health Authority QEII Health Sciences Centre	Halifax	Nova Scotia	Canada	B3H 2Y9
11	Juravinski Cancer Centre	Hamilton	Ontario	Canada	L8V 5C2
12	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
13	University Health Network - Princess Margaret Cancer Centre	Toronto	Ontario	Canada	M5G 2M9
14	Local Institution	Seoul		Korea, Republic of	03080
15	Radboud Universitair Medisch Centrum	Nijmegen		Netherlands	6525 GA
16	Local Institution	San Juan		Puerto Rico	00927

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• Investigator Inquiry Form
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02247349
• Other Study ID Numbers: CA001-030; 2014-002372-89
• First Posted: Sep 25, 2014
• Last Update Posted: Nov 19, 2021
• Last Verified: Nov 1, 2021

• Additional relevant MeSH terms: Lung Neoplasms; Small Cell Lung Carcinoma; Nivolumab

Study Results

No Results Posted as of Nov 19, 2021