Extensive-stage Small Cell Lung Cancer
Conditions
Keywords
BMS-986012, Carboplatin, Etoposide, Extensive-stage small cell lung cancer, Fucosyl, Nivolumab, Targeted SCLC therapy
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).
Interventions
BIOLOGICALBMS-986012
Specified dose on specified days
DRUGCarboplatin
Specified dose on specified days
DRUGEtoposide
Specified dose on specified days
BIOLOGICALNivolumab
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events | From first dose to 100 days post last dose, or primary cutoff date, whichever occurs first (Up to approximately 43 months) | 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. |
| Number of Participants With Serious Adverse Events | From first dose to 100 days post last dose, or primary cutoff date, whichever occurs first (Up to approximately 43 months) | 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. |
| Number of Participants With Adverse Events Leading to Discontinuation | From first dose to 100 days post last dose, or primary cutoff date, whichever occurs first (Up to approximately 43 months) | 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. |
| Number of Participants Who Died | From first dose to primary cutoff date (Up to approximately 43 months) | Number of participants who died due to any cause. |
| Progression Free Survival (PFS) Per Blinded Independent Central Review (BICR) | 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) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival Rate (PFSR) at 6 and 12 Months | 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. |
| Progression Free Survival (PFS) Per Investigator | From randomization to the date of the first documented tumor progression, or death, whichever occurs first (Up to approximately 56 months) | 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. |
| Objective Response Rate (ORR) | From randomization to the date of first documented response (Up to approximately 56 months) | 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. |
| Duration of Response (DoR) | 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) | 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 to Response (TTR) | From randomization to the date of first documented CR or PR (Up to approximately 56 months) | 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. |
| Overall Survival (OS) | From randomization to the date of death due to any cause (Up to approximately 56 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. |
| Overall Survival Rate (OSR) at 12 and 24 Months | 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. |
| Number of Participants With Anti-Nivolumab Antibody (ADA) | From baseline up to approximately 56 months | 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. |
Countries
Australia, Belgium, Canada, Greece, Italy, Japan, Netherlands, Poland, Romania, Spain, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 66.0 Years STANDARD_DEVIATION 7.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 47 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 45 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 122 Participants |
| Sex: Female, Male Female | 59 Participants |
| Sex: Female, Male Male | 43 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 50 / 67 | 56 / 68 |
| other Total, other adverse events | 62 / 66 | 62 / 65 |
| serious Total, serious adverse events | 38 / 66 | 34 / 65 |
Outcome results
None listed