Clinical trial NCT04702880: A Study of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Extensive-stage Small Cell Lung Cancer
Keywords: BMS-986012
Carboplatin
Etoposide
Extensive-stage small cell lung cancer
Fucosyl
Nivolumab
Targeted SCLC therapy
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2021-01-11
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: Up to 2 years and 100 days
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 2 years and 128 days
measure: Incidence of AEs leading to discontinuation
timeFrame: Up to 2 years and 128 days
measure: Incidence of deaths
timeFrame: Up to 2 years and 128 days
measure: Progression-free survival (PFS) by blinded independent central review (BICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
timeFrame: Up to 2 years
Secondary outcomes:
measure: Progression-free survival rate (PFSR)
timeFrame: 6 and 12 months
measure: PFS by investigator based on RECIST v1.1 criteria
timeFrame: Up to 2 years
measure: PFSR
timeFrame: 6 and 12 months
measure: Objective response rate (ORR) based on RECIST v1.1 criteria
timeFrame: Up to 2 years
measure: Time to response (TTR) based on RECIST v1.1 criteria
timeFrame: Up to 2 years
measure: Duration of response (DOR) based on RECIST v1.1 criteria
timeFrame: Up to 2 years
measure: Overall survival (OS)
timeFrame: Up to 3 years
measure: Overall survival rate (OSR)
timeFrame: Up to 3 years
measure: Immunogenicity of BMS-986012 measured by assessment of the presence of specific anti-drug antibodies (ADAs) to BMS-986012 (i.e. incidence of positive ADAs)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Local Institution - 0075
state: Alabama
city: Hackensack
country: United States
facility: Local Institution - 0022
state: New Jersey
city: Durham
country: United States
facility: Local Institution - 0002
state: North Carolina
city: Cincinnati
country: United States
facility: Local Institution - 0060
state: Ohio
city: Cincinnati
country: United States
facility: Local Institution
state: Ohio
city: Cleveland
country: United States
facility: Local Institution - 0067
state: Ohio
city: Nashville
country: United States
facility: Local Institution - 0081
state: Tennessee
city: Dallas
country: United States
facility: Local Institution
state: Texas
city: Westmead
country: Australia
facility: Local Institution - 0003
state: New South Wales
city: Greenslopes
country: Australia
facility: Local Institution - 0023
state: Queensland
city: Malvern
country: Australia
facility: Local Institution - 0001
state: Victoria
city: Murdoch
country: Australia
facility: Local Institution - 0004
state: Western Australia
city: Charleroi
country: Belgium
facility: Local Institution - 0051
city: Gent
country: Belgium
facility: Local Institution - 0034
city: Liège
country: Belgium
facility: Local Institution - 0050
city: Edmonton
country: Canada
facility: Local Institution - 0012
state: Alberta
city: Brampton
country: Canada
facility: Local Institution - 0064
state: Ontario
city: Heraklion
country: Greece
facility: Local Institution - 0045
state: Irakleío
city: Athens
country: Greece
facility: Local Institution - 0036
city: Athens
country: Greece
facility: Local Institution - 0038
city: Peschiera del Garda
country: Italy
facility: Local Institution - 0030
city: Pisa
country: Italy
facility: Local Institution - 0031
city: Rozzano
country: Italy
facility: Local Institution - 0029
city: Sendai
country: Japan
facility: Local Institution - 0073
state: Miyagi
city: Osaka-Sayama City
country: Japan
facility: Local Institution - 0070
state: Osaka
city: Takatsuki
country: Japan
facility: Local Institution - 0069
state: Osaka
city: Ina-machi
country: Japan
facility: Local Institution - 0077
state: Saitama
city: Amsterdam
country: Netherlands
facility: Local Institution - 0039
state: Noord-Holland
city: Arnhem
country: Netherlands
facility: Local Institution - 0066
city: Groningen
country: Netherlands
facility: Local Institution - 0040
city: Gdansk
country: Poland
facility: Local Institution - 0049
city: Łódź
country: Poland
facility: Local Institution - 0048
city: Bucharest
country: Romania
facility: Local Institution - 0043
city: Cluj
country: Romania
facility: Local Institution - 0042
city: Craiova
country: Romania
facility: Local Institution - 0041
city: Barcelona
country: Spain
facility: Local Institution - 0007
state: Barcelona [Barcelona]
city: Madrid
country: Spain
facility: Local Institution - 0021
city: Majadahonda
country: Spain
facility: Local Institution - 0005
city: Málaga
country: Spain
facility: Local Institution - 0006
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: 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.