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

Bristol-Myers Squibb135 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

135

Conditions

Extensive-stage Small Cell Lung Cancer

Interventions

BMS-986012BIOLOGICAL

Specified dose on specified days

CarboplatinDRUG

Specified dose on specified days

EtoposideDRUG

Specified dose on specified days

Nivolumab

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (39)

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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)

Data from ClinicalTrials.gov

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Local Institution - 0075

Birmingham, Alabama, United States

Local Institution - 0022

Hackensack, New Jersey, United States

Local Institution - 0002

Durham, North Carolina, United States

Local Institution - 0060

Cincinnati, Ohio, United States

Local Institution

Cincinnati, Ohio, United States

Local Institution - 0067

Cleveland, Ohio, United States

Local Institution - 0081

Nashville, Tennessee, United States

Local Institution

Dallas, Texas, United States

Local Institution - 0003

Westmead, New South Wales, Australia

Local Institution - 0023

Greenslopes, Queensland, Australia

...and 29 more locations

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: From baseline up to approximately 56 months