Brief Summary
The purpose of this study is to assess the safety profile of relatlimab plus nivolumab in combination with platinum doublet chemotherapy (PDCT) and to determine if nivolumab plus relatlimab in combination with PDCT improves overall response rate (ORR) when compared to nivolumab plus PDCT in participants with previously untreated Stage IV or recurrent non-small cell lung cancer (NSCLC).
Brief Title
A Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)
Completion Date
Completion Date Type
Estimated
Conditions
Non-small Cell Lung Cancer
Recurrent Non-small Cell Lung Cancer
Metastatic Non-small Cell Lung Cancer
Eligibility Criteria
Inclusion Criteria
* Histologically confirmed metastatic non-small cell lung cancer (NSCLC) of squamous (SQ) or non-squamous (NSQ) histology with Stage IV A/B (as defined by the 8th International Association for the Study of Lung Cancer Classification) or recurrent disease following multi-modal therapy for locally advanced disease.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than or equal to 1 at screening and confirmed prior to randomization.
* Measurable disease by computed tomography (CT) or magnetic resonance resources (MRI) per response evaluation criteria in solid tumor version 1.1 (RECIST 1.1) criteria.
* No prior systemic anti-cancer treatment (including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors) given as primary therapy for advanced or metastatic disease.
Exclusion Criteria
* Participants with EGFR, ALK, ROS-1, or known B-rapidly accelerated fibrosarcoma proto-oncogene (BRAF V600E) mutations that are sensitive to available targeted therapy.
* Untreated CNS metastases.
* Leptomeningeal metastases (carcinomatous meningitis).
* Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to randomization (ie, participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before randomization and the participant has no evidence of disease).
* Prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-programmed death-ligand 2 (PD-L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
* Other protocol-defined Inclusion/Exclusion criteria apply.
* Histologically confirmed metastatic non-small cell lung cancer (NSCLC) of squamous (SQ) or non-squamous (NSQ) histology with Stage IV A/B (as defined by the 8th International Association for the Study of Lung Cancer Classification) or recurrent disease following multi-modal therapy for locally advanced disease.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than or equal to 1 at screening and confirmed prior to randomization.
* Measurable disease by computed tomography (CT) or magnetic resonance resources (MRI) per response evaluation criteria in solid tumor version 1.1 (RECIST 1.1) criteria.
* No prior systemic anti-cancer treatment (including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors) given as primary therapy for advanced or metastatic disease.
Exclusion Criteria
* Participants with EGFR, ALK, ROS-1, or known B-rapidly accelerated fibrosarcoma proto-oncogene (BRAF V600E) mutations that are sensitive to available targeted therapy.
* Untreated CNS metastases.
* Leptomeningeal metastases (carcinomatous meningitis).
* Concurrent malignancy requiring treatment or history of prior malignancy active within 2 years prior to randomization (ie, participants with a history of prior malignancy are eligible if treatment was completed at least 2 years before randomization and the participant has no evidence of disease).
* Prior treatment with an anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), anti-programmed death-ligand 2 (PD-L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
* Other protocol-defined Inclusion/Exclusion criteria apply.
Inclusion Criteria
Inclusion Criteria
* Histologically confirmed metastatic non-small cell lung cancer (NSCLC) of squamous (SQ) or non-squamous (NSQ) histology with Stage IV A/B (as defined by the 8th International Association for the Study of Lung Cancer Classification) or recurrent disease following multi-modal therapy for locally advanced disease.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than or equal to 1 at screening and confirmed prior to randomization.
* Measurable disease by computed tomography (CT) or magnetic resonance resources (MRI) per response evaluation criteria in solid tumor version 1.1 (RECIST 1.1) criteria.
* No prior systemic anti-cancer treatment (including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors) given as primary therapy for advanced or metastatic disease.
Inclusion/
* Histologically confirmed metastatic non-small cell lung cancer (NSCLC) of squamous (SQ) or non-squamous (NSQ) histology with Stage IV A/B (as defined by the 8th International Association for the Study of Lung Cancer Classification) or recurrent disease following multi-modal therapy for locally advanced disease.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) of less than or equal to 1 at screening and confirmed prior to randomization.
* Measurable disease by computed tomography (CT) or magnetic resonance resources (MRI) per response evaluation criteria in solid tumor version 1.1 (RECIST 1.1) criteria.
* No prior systemic anti-cancer treatment (including epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) inhibitors) given as primary therapy for advanced or metastatic disease.
Inclusion/
Gender
All
Gender Based
false
Keywords
Stage IV Non-small Cell Lunch Cancer
Recurrent Non-small Cell Lung Cancer
Metastatic Non-small Cell Lung Cancer
Relatlimab
Nivolumab
Chemotherapy
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT04623775
Org Class
Industry
Org Full Name
Bristol-Myers Squibb
Org Study Id
CA224-104
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
A Phase 2 Randomized Study of Relatlimab Plus Nivolumab in Combination With Chemotherapy vs. Nivolumab in Combination With Chemotherapy as First Line Treatment for Participants With Stage IV or Recurrent Non-small Cell Lung Cancer (NSCLC)
Primary Outcomes
Outcome Description
Percentage of participants with treatment related adverse events (TRAEs) leading to discontinuation within 12 weeks of first dose.
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0.
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0.
Outcome Measure
TRAEs Leading to Discontinuation Within 12 Weeks of First Dose in Part 1
Outcome Time Frame
from first dose to 12 weeks after first dose
Outcome Description
Objective Response Rate (ORR) per RECIST v1.1 by BICR is defined as the number of participants in the randomized population who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1) divided by the number of participants in the population. BOR is defined as the best response, as determined by the BICR, recorded between the date of randomization and the date of first objectively documented progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first.
Outcome Measure
ORR Per RECISTS v1.1 by BICR in Part 2
Outcome Time Frame
Approximately 14.8 Months
Secondary Ids
Secondary Id
2020-004026-31
Secondary Id
U1111-1256-8115
Secondary Outcomes
Outcome Description
Number of participants with treatment related adverse events (TRAEs) leading to discontinuation based on grade.
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0
Outcome Time Frame
From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)
Outcome Measure
TRAEs Leading to Discontinuation in Part 1
Outcome Description
Number of participants with a treatment related AE in part 1.
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0
Outcome Time Frame
From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)
Outcome Measure
Number of Participants With a Treatment Related AEs in Part 1
Outcome Description
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose, results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event (defined as a medical event(s) that may not be immediately life-threatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention \[e.g., medical, surgical\] to prevent one of the other serious outcomes listed in the definition).
Grading will be determined for severity according to the NCI CTCAE v5.0.
Grading will be determined for severity according to the NCI CTCAE v5.0.
Outcome Time Frame
From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)
Outcome Measure
Number of Participants With Treatment Releted SAEs in Part 1
Outcome Description
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Select Adverse Events (AEs) will be determined for severity according to the NCI CTCAE v5.0.
Select Adverse Events (AEs) will be determined for severity according to the NCI CTCAE v5.0.
Outcome Time Frame
From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)
Outcome Measure
Number of Participants With Treatment Releted Select AEs in Part 1
Outcome Description
Objective Response Rate (ORR) per RECIST v1.1 by BICR is defined as the number of participants in the randomized population who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1) divided by the number of participants in the population. BOR is defined as the best response, as determined by the BICR, recorded between the date of randomization and the date of first objectively documented progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first.
Outcome Time Frame
Approximately 14.8 Months
Outcome Measure
ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2
Outcome Description
Duration of Response (DOR) will be assessed by BICR. It is defined as the time between the date of first documented response (CR or PR) that is subsequently confirmed, to the date of the first objectively documented tumor progression as determined by the BICR (per RECIST v1.1), or death due to any cause, whichever occurs first.
Outcome Time Frame
Approximately up to 13.7 months
Outcome Measure
DoR Per RECISTS v1.1 by BICR in Part 2
Outcome Description
Number of participants with an adverse event (AE).
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0.
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0.
Outcome Time Frame
From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)
Outcome Measure
Number of Participants With a AE in Part 2
Outcome Description
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Grading will be determined for severity according to the NCI CTCAE v5.0.
Grading will be determined for severity according to the NCI CTCAE v5.0.
Outcome Time Frame
From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)
Outcome Measure
Number of Participants With a Treatment Related AEs in Part 2
Outcome Description
SAE is defined as a life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe). SAEs can also result in death. The AE requires inpatient hospitalization or causes prolongation of existing hospitalization. Results in persistent or significant disability/incapacity. Is a congenital anomaly/birth defect. Is an important medical event (defined as a medical event(s) that may not be immediately lifethreatening or result in death or hospitalization but, based upon appropriate medical and scientific judgment, may jeopardize the participant or may require intervention \[e.g., medical, surgical\] to prevent one of the other serious outcomes listed in the definition above.)
Grading will be determined for severity according to the NCI CTCAE v5.0.
Grading will be determined for severity according to the NCI CTCAE v5.0.
Outcome Time Frame
From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)
Outcome Measure
Number of Participants With a Treatment Related SAEs in Part 2
Outcome Description
IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.
Grading will be determined for severity according to the NCI CTCAE v5.0.
Grading will be determined for severity according to the NCI CTCAE v5.0.
Outcome Time Frame
From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)
Outcome Measure
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2
Outcome Description
Objective Response Rate (ORR) per RECIST v1.1 by BICR is defined as the number of participants in the randomized population who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1) divided by the number of participants in the population. BOR is defined as the best response, as determined by the BICR, recorded between the date of randomization and the date of first objectively documented progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first.
Outcome Time Frame
On Going
Outcome Measure
ORR by LAG-3 Expression Per RECISTS v1.1 by BICR in Part 2
Outcome Description
Objective Response Rate (ORR) per RECIST v1.1 by BICR is defined as the number of participants in the randomized population who achieve a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) based on BICR assessments (using RECIST v1.1) divided by the number of participants in the population. BOR is defined as the best response, as determined by the BICR, recorded between the date of randomization and the date of first objectively documented progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first.
Outcome Time Frame
Ongoing
Outcome Measure
ORR by FG-L1 Expression Per RECISTS v1.1 by BICR in Part 2
Outcome Description
Progression Free Survival is defined as the time between the date of randomization and the first date of documented progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first.
Outcome Time Frame
Ongoing
Outcome Measure
PFS Per RECISTS v1.1 by BICR in Part 2
Outcome Description
Progression Free Survival is defined as the time between the date of randomization and the first date of documented progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first.
Outcome Time Frame
Ongoing
Outcome Measure
PFS by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2
Outcome Description
Progression Free Survival is defined as the time between the date of randomization and the first date of documented progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first.
Outcome Time Frame
Ongoing
Outcome Measure
PFS by LAG-3 Expression Per RECISTS v1.1 by BICR in Part 2
Outcome Description
Progression Free Survival is defined as the time between the date of randomization and the first date of documented progression, based on BICR assessments (per RECIST v1.1), or death due to any cause, whichever occurs first.
Outcome Time Frame
Ongoing
Outcome Measure
PFS by FG-L1 Expression Per RECISTS v1.1 by BICR in Part 2
Outcome Description
AE is defined as any new untoward medical occurrence or worsenig of a preexising medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Select Adverse Events (AEs) will be determined for severity according to the NCI CTCAE v5.0.
Select Adverse Events (AEs) will be determined for severity according to the NCI CTCAE v5.0.
Outcome Time Frame
Ongoing
Outcome Measure
Number of Participants With Treatment Releted Select AEs in Part 2
See Also Links
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Balazs Halmos
Investigator Email
bahalmos@montefiore.org
Categories Mesh Debug
Lung & Chest Cancers --- CARCINOMA, NON-SMALL-CELL LUNG
Lung & Chest Cancers --- CARCINOMA, BRONCHOGENIC
Lung & Chest Cancers --- BRONCHIAL NEOPLASMS
Lung & Chest Cancers --- LUNG NEOPLASMS
Lung & Chest Cancers --- RESPIRATORY TRACT NEOPLASMS
Lung & Chest Cancers --- THORACIC NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Lung & Chest Cancers --- LUNG DISEASES
COVID-19 --- LUNG DISEASES
Lung --- LUNG DISEASES
Asthma and Other Respiratory Diseases --- RESPIRATORY TRACT DISEASES
Lung & Chest Cancers --- RESPIRATORY TRACT DISEASES
COVID-19 --- RESPIRATORY TRACT DISEASES
Lung --- RESPIRATORY TRACT DISEASES
MeSH Terms
CARCINOMA, NON-SMALL-CELL LUNG
CARCINOMA, BRONCHOGENIC
BRONCHIAL NEOPLASMS
LUNG NEOPLASMS
RESPIRATORY TRACT NEOPLASMS
THORACIC NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
LUNG DISEASES
RESPIRATORY TRACT DISEASES
NIVOLUMAB
RELATLIMAB
CARBOPLATIN
CISPLATIN
PACLITAXEL
130-NM ALBUMIN-BOUND PACLITAXEL
PEMETREXED
ANTIBODIES, MONOCLONAL, HUMANIZED
ANTIBODIES, MONOCLONAL
ANTIBODIES
IMMUNOGLOBULINS
IMMUNOPROTEINS
BLOOD PROTEINS
PROTEINS
AMINO ACIDS, PEPTIDES, AND PROTEINS
SERUM GLOBULINS
GLOBULINS
COORDINATION COMPLEXES
ORGANIC CHEMICALS
CHLORINE COMPOUNDS
INORGANIC CHEMICALS
NITROGEN COMPOUNDS
PLATINUM COMPOUNDS
TAXOIDS
CYCLODECANES
CYCLOPARAFFINS
HYDROCARBONS, ALICYCLIC
HYDROCARBONS, CYCLIC
HYDROCARBONS
DITERPENES
TERPENES
GUANINE
HYPOXANTHINES
PURINONES
PURINES
HETEROCYCLIC COMPOUNDS, 2-RING
HETEROCYCLIC COMPOUNDS, FUSED-RING
HETEROCYCLIC COMPOUNDS
GLUTAMATES
AMINO ACIDS, ACIDIC
AMINO ACIDS
AMINO ACIDS, DICARBOXYLIC