A Study of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer

A Randomized, Open-label Phase 2 Clinical Trial of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer

The purpose of this study is to demonstrate that treatment with BMS-986012 in combination with carboplatin, etoposide, and nivolumab will have acceptable safety and tolerability and will improve progression-free survival compared with carboplatin, etoposide, and nivolumab alone in newly diagnosed participants with extensive-stage small cell lung cancer (ES-SCLC).

Study Overview

• Status: Completed
• Conditions: Extensive-stage Small Cell Lung Cancer
• Intervention / Treatment: Biological: Nivolumab; Drug: Carboplatin; Biological: BMS-986012; Drug: Etoposide

• Study Type: Interventional
• Enrollment (Actual): 135
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Local Institution - 0003
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
      • Local Institution - 0023
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • Local Institution - 0001
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Local Institution - 0004
• Belgium
  • Ghent, Belgium, 9000
    • Local Institution - 0034
  • Liège, Belgium, 4000
    • Local Institution - 0050
  • Hainaut
    • Charleroi, Hainaut, Belgium, 6060
      • Local Institution - 0051
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Local Institution - 0012
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Local Institution - 0064
• Greece
  • Athens, Greece, 11527
    • Local Institution - 0036
  • Athens, Greece, 185 47
    • Local Institution - 0038
  • Irakleío
    • Heraklion, Irakleío, Greece, 715 00
      • Local Institution - 0045
• Italy
  • Peschiera del Garda, Italy, 37019
    • Local Institution - 0030
  • Pisa, Italy, 56124
    • Local Institution - 0031
  • Rozzano, Italy, 20089
    • Local Institution - 0029
• Japan
  • Miyagi
    • Sendai, Miyagi, Japan, 980-0873
      • Local Institution - 0073
  • Osaka
    • Takatsuki, Osaka, Japan, 5698686
      • Local Institution - 0069
    • Ōsaka-sayama, Osaka, Japan, 589-8511
      • Local Institution - 0070
  • Saitama
    • Ina-machi, Saitama, Japan, 362-0806
      • Local Institution - 0077
• Netherlands
  • Arnhem, Netherlands, 6815 AD
    • Local Institution - 0066
  • Groningen, Netherlands, 9700RB
    • Local Institution - 0040
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Local Institution - 0039
• Poland
  • Gdansk, Poland, 80-214
    • Local Institution - 0049
  • Lodz, Poland, 93-338
    • Local Institution - 0048
• Romania
  • Bucharest, Romania, 022328
    • Local Institution - 0043
  • Cluj-Napoca, Romania, 400015
    • Local Institution - 0042
  • Craiova, Romania, 200542
    • Local Institution - 0041
• Spain
  • Madrid, Spain, 28041
    • Local Institution - 0021
  • Majadahonda, Spain, 28222
    • Local Institution - 0005
  • Málaga, Spain, 29010
    • Local Institution - 0006
  • Barcelona [Barcelona]
    • Barcelona, Barcelona [Barcelona], Spain, 08035
      • Local Institution - 0007
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • Local Institution - 0075
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Local Institution - 0022
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Local Institution - 0002
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Local Institution
    • Cincinnati, Ohio, United States, 45267
      • Local Institution - 0060
    • Cleveland, Ohio, United States, 44106-1716
      • Local Institution - 0067
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 0081
  • Texas
    • Dallas, Texas, United States, 75390
      • Local Institution

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC) and extensive-stage disease (American Joint Committee on Cancer, 8th edition, Stage IV [T any, N any, M1a, M1b, or M1c], or T3-4 due to multiple lung nodules that are too extensive or tumor or nodal volume that is too large to be encompassed in a tolerable radiation plan)
• Participants taking part in the separate PET tracer sub-study must provide a fresh tumor biopsy from any disease site (primary or metastatic)
• Archived tumor specimens, in the form of blocks or sectioned slides, are mandatory for all participants except those participating in the separate PET tracer sub-study for whom the archived tumor specimen is optional
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1
• At least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria
• Adequate hematologic and end organ function
• Must agree to follow specific methods of contraception, if applicable

Exclusion Criteria:

• Women who are pregnant or breastfeeding. Japan only: participation in the study is not allowed even if breastfeeding is suspended
• Prior chemotherapy, radiation therapy, or biologic therapy for SCLC. Previously treated limited stage SCLC (LS-SCLC) participants are also excluded
• Symptomatic brain or other central nervous system (CNS) metastases
• Paraneoplastic autoimmune syndrome requiring systemic treatment
• History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan
• Grade ≥ 2 peripheral sensory neuropathy at study entry
• Significant uncontrolled cardiovascular disease
• Active, known or suspected autoimmune disease or inflammatory disorder

Other protocol-defined inclusion/exclusion criteria apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Carboplatin + Etoposide + Nivolumab + BMS-986012	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Drug: Carboplatin; Specified dose on specified days; Biological: BMS-986012; Specified dose on specified days; Other Names: Fucosyl-GM1 Antibody; Drug: Etoposide; Specified dose on specified days
Experimental: Arm B: Carboplatin + Etoposide + Nivolumab	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558; Drug: Carboplatin; Specified dose on specified days; Drug: Etoposide; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	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 treatment that does not necessarily have a causal relationship with this treatment.	From first dose to 100 days post last dose, or primary cutoff date, whichever occurs first (Up to approximately 43 months)
Number of Participants With Serious Adverse Events	Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, and requires inpatient hospitalization or causes prolongation of existing hospitalization.	From first dose to 100 days post last dose, or primary cutoff date, whichever occurs first (Up to approximately 43 months)
Number of Participants With Adverse Events 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 treatment that does not necessarily have a causal relationship with this treatment.	From first dose to 100 days post last dose, or primary cutoff date, whichever occurs first (Up to approximately 43 months)
Number of Participants Who Died	Number of participants who died due to any cause.	From first dose to primary cutoff date (Up to approximately 43 months)
Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR)	PFS based on RECIST v1.1 is defined as the time from randomization to the date of the first documented tumor progression by BICR or death from any cause. Estimates are based on Kaplan-Meier product-limit method. Progressive disease=At least a 20% increase in the sum of diameters of target lesions.	From randomization to the date of the first documented tumor progression, or death, or primary cutoff date, whichever occurs first (Up to approximately 50 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Rate (PFSR) at 6 and 12 Months	PFSR is defined as the percentage of participants progression free at 6 and 12 months. PFS based on RECIST v1.1 is defined as the time from randomization to the date of the first documented tumor progression by Blinded Independent Central Review (BICR) and by investigator, or death from any cause. Progressive disease=At least a 20% increase in the sum of diameters of target lesions.	6 and 12 months
Progression Free Survival (PFS) Per Investigator	PFS based on RECIST v1.1 is defined as the time from randomization to the date of the first documented tumor progression by Investigator or death from any cause. Estimates are based on Kaplan-Meier product-limit method. Progressive disease=At least a 20% increase in the sum of diameters of target lesions.	From randomization to the date of the first documented tumor progression, or death, whichever occurs first (Up to approximately 56 months)
Objective Response Rate (ORR)	ORR per Blinded Independent Central Review (BICR) and per investigator is defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR=Disappearance of all target lesions. PR=At least 30% decrease in the sum of diameters of target lesions.	From randomization to the date of first documented response (Up to approximately 56 months)
Duration of Response (DoR)	DoR per Blinded Independent Central Review and per investigator is defined for participants who have a confirmed CR or PR as the date from first documented CR or PR per RECIST v1.1 to the date of the documentation of disease progression or death due to any cause, whichever is earlier. CR=Disappearance of all target lesions. PR=At least 30% decrease in the sum of diameters of target lesions.	From randomization to the date of the documentation of disease progression or death due to any cause, whichever is earlier (Up to approximately 56 months)
Time to Response (TTR)	TTR per Blinded Independent Central Review (BICR) and per investigator is defined for participants who had a confirmed CR or PR as the time from the date of randomization to date of first documented CR or PR per RECIST v1.1. CR=Disappearance of all target lesions. PR=At least 30% decrease in the sum of diameters of target lesions.	From randomization to the date of first documented CR or PR (Up to approximately 56 months)
Overall Survival (OS)	OS is defined as the time from randomization to the time of death due to any cause. OS will be estimated using the Kaplan-Meier method.	From randomization to the date of death due to any cause (Up to approximately 56 months)
Overall Survival Rate (OSR) at 12 and 24 Months	OSR is defined as the percentage of participants surviving at 12 and 24 months. OS is defined as the time from randomization to the time of death due to any cause. OS will be estimated using the Kaplan-Meier method.	12 and 24 months
Number of Participants With Anti-Nivolumab Antibody (ADA)	ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (>=) than baseline positive titer) at any time after initiation of treatment. Baseline ADA Positive: A participant with baseline ADA-positive sample.	From baseline up to approximately 56 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Chu Q, Leighl NB, Surmont V, van Herpen C, Sibille A, Markman B, Clarke S, Juergens RA, Rivera MA, Andelkovic V, Rudin CM, Snow S, Kim DW, Sanatani M, Lin H, Sanghavi K, Tannenbaum-Dvir S, Basciano P, Lathers D, Urbanska K, Kollia G, He C, DiPiero A, Liu Y, Ready N. BMS-986012, an Anti-Fucosyl-GM1 Monoclonal Antibody as Monotherapy or in Combination With Nivolumab in Relapsed/Refractory SCLC: Results From a First-in-Human Phase 1/2 Study. JTO Clin Res Rep. 2022 Aug 27;3(11):100400. doi: 10.1016/j.jtocrr.2022.100400. eCollection 2022 Nov.

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Actual): May 22, 2025
• Study Completion (Actual): November 28, 2025

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: January 7, 2021
• First Posted (Actual): January 11, 2021

Study Record Updates

• Last Update Posted (Actual): June 17, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Nivolumab; Carboplatin; Etoposide; BMS-986012; Extensive-stage small cell lung cancer; Fucosyl; Targeted SCLC therapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Coordination Complexes; Nivolumab; Etoposide; Carboplatin
• Other Study ID Numbers: CA001-050; 2020-001863-10 (EudraCT Number); U1111-1250-4427 (Registry Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: BMS will provide access to individual anonymized participant data upon request from qualified researchers, and subject to certain criteria. Additional information regarding Bristol Myer Squibb's data sharing policy and process can be found at https://www.bms.com/researchers-and-partners/clinical-trials-and-research.html
• IPD Sharing Time Frame: See Plan Description
• IPD Sharing Access Criteria: See Plan Description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No