Metastatic Non-small Cell Lung Cancer, Non-small Cell Lung Cancer, Recurrent Non-small Cell Lung Cancer
Conditions
Keywords
Stage IV Non-small Cell Lunch Cancer, Recurrent Non-small Cell Lung Cancer, Metastatic Non-small Cell Lung Cancer, Relatlimab, Nivolumab, Chemotherapy
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).
Interventions
DRUGCisplatin
Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
DRUGPaclitaxel
Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
DRUGNab-Paclitaxel
Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
DRUGPemetrexed
Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
BIOLOGICALNivolumab
Specified dose on specified days
BIOLOGICALRelatlimab
Specified dose on specified days
DRUGCarboplatin
Specified dose on specified days. Participant will receive only two of the listed chemotherapies (carboplatin, cisplatin, paclitaxel, nab-paclitaxel) along with immunotherapy.
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TRAEs Leading to Discontinuation Within 12 Weeks of First Dose in Part 1 | from first dose to 12 weeks after first dose | 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. |
| ORR Per RECISTS v1.1 by BICR in Part 2 | Approximately 14.8 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TRAEs Leading to Discontinuation in Part 1 | From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months) | 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 |
| Number of Participants With a Treatment Related AEs in Part 1 | From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months) | 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 |
| Number of Participants With Treatment Releted SAEs in Part 1 | From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months) | 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. |
| Number of Participants With Treatment Releted Select AEs in Part 1 | From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months) | 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. |
| ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | Approximately 14.8 Months | 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. |
| DoR Per RECISTS v1.1 by BICR in Part 2 | Approximately up to 13.7 months | 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. |
| Number of Participants With a AE in Part 2 | From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months) | 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. |
| Number of Participants With a Treatment Related AEs in Part 2 | From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months) | 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. |
| Number of Participants With a Treatment Related SAEs in Part 2 | From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months) | 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. |
| Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months) | 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. |
| ORR by LAG-3 Expression Per RECISTS v1.1 by BICR in Part 2 | On Going | 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. |
| ORR by FG-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | Ongoing | 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. |
| PFS Per RECISTS v1.1 by BICR in Part 2 | Ongoing | 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. |
| PFS by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | Ongoing | 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. |
| PFS by LAG-3 Expression Per RECISTS v1.1 by BICR in Part 2 | Ongoing | 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. |
| PFS by FG-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | Ongoing | 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. |
| Number of Participants With Treatment Releted Select AEs in Part 2 | Ongoing | 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Chile, France, Germany, Ireland, Italy, Mexico, Netherlands, Poland, Romania, Russia, Spain, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORBristol-Myers Squibb
Bristol-Myers Squibb
Participant flow
Pre-assignment details
468 Randomized and 463 Treated
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Treatment A Nivo 360mg Q3W + Rela 720mg Q3W + Histology Based PDCT | 79 |
| Part 1: Treatment B Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT | 80 |
| Part 2: Treatment C Nivo 360mg Q3W + Rela 360mg Q3W + Histology Based PDCT | 158 |
| Part 2: Treatment D Nivo 360mg Q3W + Histology Based PDCT | 151 |
| Total | 468 |
Baseline characteristics
| Characteristic | Part 1: Treatment A | Part 1: Treatment B | Part 2: Treatment C | Part 2: Treatment D | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 42 Participants | 38 Participants | 85 Participants | 79 Participants | 244 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 42 Participants | 73 Participants | 72 Participants | 224 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants | 12 Participants | 31 Participants | 28 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 44 Participants | 91 Participants | 88 Participants | 260 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 26 Participants | 24 Participants | 36 Participants | 35 Participants | 121 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 2 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 3 Participants | 8 Participants | 7 Participants | 21 Participants |
| Race (NIH/OMB) White | 75 Participants | 77 Participants | 148 Participants | 141 Participants | 441 Participants |
| Sex: Female, Male Female | 28 Participants | 32 Participants | 55 Participants | 57 Participants | 172 Participants |
| Sex: Female, Male Male | 51 Participants | 48 Participants | 103 Participants | 94 Participants | 296 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 47 / 77 | 46 / 79 | 79 / 158 | 70 / 149 |
| other Total, other adverse events | 74 / 77 | 78 / 79 | 151 / 158 | 145 / 149 |
| serious Total, serious adverse events | 46 / 77 | 52 / 79 | 103 / 158 | 81 / 149 |
Outcome results
Primary
ORR Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: Approximately 14.8 Months
Population: All randomized participants in Part 2
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Treatment A | ORR Per RECISTS v1.1 by BICR in Part 2 | 50.6 Percentage of Participants |
| Part 1: Treatment B | ORR Per RECISTS v1.1 by BICR in Part 2 | 43.0 Percentage of Participants |
90% CI: [0.94, 2.05]Cochran-Mantel-Haenszel
Primary
TRAEs Leading to Discontinuation Within 12 Weeks of First Dose in Part 1
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.
Time frame: from first dose to 12 weeks after first dose
Population: All Treated Dose-Safety Evaluable participants in part 1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: Treatment A | TRAEs Leading to Discontinuation Within 12 Weeks of First Dose in Part 1 | 5.6 Percentage of Participants |
| Part 1: Treatment B | TRAEs Leading to Discontinuation Within 12 Weeks of First Dose in Part 1 | 12.1 Percentage of Participants |
95% CI: [-16, 3]
Secondary
DoR Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: Approximately up to 13.7 months
Population: All randomized participants in Part 2
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part 1: Treatment A | DoR Per RECISTS v1.1 by BICR in Part 2 | 8.41 Months |
| Part 1: Treatment B | DoR Per RECISTS v1.1 by BICR in Part 2 | 7.10 Months |
Secondary
Number of Participants With a AE in Part 2
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.
Time frame: From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)
Population: All treated participants in Part 2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Treatment A | Number of Participants With a AE in Part 2 | Any Grade | 158 Participants |
| Part 1: Treatment A | Number of Participants With a AE in Part 2 | Grade 3 to 4 | 90 Participants |
| Part 1: Treatment A | Number of Participants With a AE in Part 2 | Grade 5 | 26 Participants |
| Part 1: Treatment B | Number of Participants With a AE in Part 2 | Any Grade | 147 Participants |
| Part 1: Treatment B | Number of Participants With a AE in Part 2 | Grade 3 to 4 | 85 Participants |
| Part 1: Treatment B | Number of Participants With a AE in Part 2 | Grade 5 | 19 Participants |
Secondary
Number of Participants With a Treatment Related AEs in Part 1
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
Time frame: From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)
Population: All treated participants in Part 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Treatment A | Number of Participants With a Treatment Related AEs in Part 1 | 75 Participants |
| Part 1: Treatment B | Number of Participants With a Treatment Related AEs in Part 1 | 76 Participants |
Secondary
Number of Participants With a Treatment Related AEs in Part 2
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.
Time frame: From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)
Population: All treated participants in Part 2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Treatment A | Number of Participants With a Treatment Related AEs in Part 2 | Any Grade | 147 Participants |
| Part 1: Treatment A | Number of Participants With a Treatment Related AEs in Part 2 | Grade 3 to 4 | 79 Participants |
| Part 1: Treatment A | Number of Participants With a Treatment Related AEs in Part 2 | Grade 5 | 4 Participants |
| Part 1: Treatment B | Number of Participants With a Treatment Related AEs in Part 2 | Grade 5 | 4 Participants |
| Part 1: Treatment B | Number of Participants With a Treatment Related AEs in Part 2 | Any Grade | 138 Participants |
| Part 1: Treatment B | Number of Participants With a Treatment Related AEs in Part 2 | Grade 3 to 4 | 78 Participants |
Secondary
Number of Participants With a Treatment Related SAEs in Part 2
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.
Time frame: From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)
Population: All treated participants in Part 2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Treatment A | Number of Participants With a Treatment Related SAEs in Part 2 | Any Grade | 34 Participants |
| Part 1: Treatment A | Number of Participants With a Treatment Related SAEs in Part 2 | Grade 3 to 4 | 26 Participants |
| Part 1: Treatment A | Number of Participants With a Treatment Related SAEs in Part 2 | Grade 5 | 4 Participants |
| Part 1: Treatment B | Number of Participants With a Treatment Related SAEs in Part 2 | Any Grade | 36 Participants |
| Part 1: Treatment B | Number of Participants With a Treatment Related SAEs in Part 2 | Grade 3 to 4 | 28 Participants |
| Part 1: Treatment B | Number of Participants With a Treatment Related SAEs in Part 2 | Grade 5 | 4 Participants |
Secondary
Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2
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.
Time frame: From first dose to 30 days post last dose of study therapy (Approximately 14.8 Months)
Population: All treated participants in Part 2
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Treatment A | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Hypothyroidism | 21 Participants |
| Part 1: Treatment A | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Diabetes Mellitus | 1 Participants |
| Part 1: Treatment A | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Hypothyroidism/Thyroiditis | 22 Participants |
| Part 1: Treatment A | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Hyperthyroidism | 14 Participants |
| Part 1: Treatment A | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Thyroiditis | 2 Participants |
| Part 1: Treatment A | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Hypophysitis | 0 Participants |
| Part 1: Treatment A | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Adrenal Insufficiency | 2 Participants |
| Part 1: Treatment B | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Hypophysitis | 1 Participants |
| Part 1: Treatment B | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Adrenal Insufficiency | 3 Participants |
| Part 1: Treatment B | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Hypothyroidism/Thyroiditis | 13 Participants |
| Part 1: Treatment B | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Hypothyroidism | 13 Participants |
| Part 1: Treatment B | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Thyroiditis | 0 Participants |
| Part 1: Treatment B | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Diabetes Mellitus | 0 Participants |
| Part 1: Treatment B | Number of Participants With Endocrine Immune-mediated Adverse Events in Part 2 | Hyperthyroidism | 3 Participants |
Secondary
Number of Participants With Treatment Releted SAEs in Part 1
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.
Time frame: From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)
Population: All treated participants in Part 1
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Treatment A | Number of Participants With Treatment Releted SAEs in Part 1 | Any Grade | 20 Participants |
| Part 1: Treatment A | Number of Participants With Treatment Releted SAEs in Part 1 | Grade 3 to 4 | 14 Participants |
| Part 1: Treatment A | Number of Participants With Treatment Releted SAEs in Part 1 | Grade 5 | 2 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted SAEs in Part 1 | Any Grade | 24 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted SAEs in Part 1 | Grade 3 to 4 | 18 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted SAEs in Part 1 | Grade 5 | 4 Participants |
Secondary
Number of Participants With Treatment Releted Select AEs 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. Select Adverse Events (AEs) will be determined for severity according to the NCI CTCAE v5.0.
Time frame: From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)
Population: All treated participants in Part 1
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Treatment A | Number of Participants With Treatment Releted Select AEs in Part 1 | Gastrointestinal | 18 Participants |
| Part 1: Treatment A | Number of Participants With Treatment Releted Select AEs in Part 1 | Hepatic | 26 Participants |
| Part 1: Treatment A | Number of Participants With Treatment Releted Select AEs in Part 1 | Pulmonary | 4 Participants |
| Part 1: Treatment A | Number of Participants With Treatment Releted Select AEs in Part 1 | Renal | 9 Participants |
| Part 1: Treatment A | Number of Participants With Treatment Releted Select AEs in Part 1 | Skin | 24 Participants |
| Part 1: Treatment A | Number of Participants With Treatment Releted Select AEs in Part 1 | Hypersensitivity/Infusion Reaction | 5 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted Select AEs in Part 1 | Skin | 18 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted Select AEs in Part 1 | Gastrointestinal | 15 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted Select AEs in Part 1 | Renal | 4 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted Select AEs in Part 1 | Hepatic | 18 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted Select AEs in Part 1 | Hypersensitivity/Infusion Reaction | 2 Participants |
| Part 1: Treatment B | Number of Participants With Treatment Releted Select AEs in Part 1 | Pulmonary | 5 Participants |
Secondary
Number of Participants With Treatment Releted Select AEs in Part 2
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.
Time frame: Ongoing
Secondary
ORR by FG-L1 Expression Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: Ongoing
Secondary
ORR by LAG-3 Expression Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: On Going
Secondary
ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: Approximately 14.8 Months
Population: All randomized participants in Part 2
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: Treatment A | ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | PD-L1 <1% | 48.6 Percentage of Participants |
| Part 1: Treatment A | ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | PD-L1 >= 1% | 53.2 Percentage of Participants |
| Part 1: Treatment A | ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | Not Quantifiable | 44.4 Percentage of Participants |
| Part 1: Treatment B | ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | PD-L1 <1% | 44.8 Percentage of Participants |
| Part 1: Treatment B | ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | PD-L1 >= 1% | 39.4 Percentage of Participants |
| Part 1: Treatment B | ORR by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2 | Not Quantifiable | 53.8 Percentage of Participants |
Secondary
PFS by FG-L1 Expression Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: Ongoing
Secondary
PFS by LAG-3 Expression Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: Ongoing
Secondary
PFS by PD-L1 Expression Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: Ongoing
Secondary
PFS Per RECISTS v1.1 by BICR in Part 2
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.
Time frame: Ongoing
Secondary
TRAEs Leading to Discontinuation in Part 1
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
Time frame: From first dose to 30 days post last dose of study therapy (Approximately 32.8 Months)
Population: All treated participants in Part 1
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1: Treatment A | TRAEs Leading to Discontinuation in Part 1 | Any Grade | 21 Participants |
| Part 1: Treatment A | TRAEs Leading to Discontinuation in Part 1 | Grade 3 to 4 | 13 Participants |
| Part 1: Treatment A | TRAEs Leading to Discontinuation in Part 1 | Grade 5 | 1 Participants |
| Part 1: Treatment B | TRAEs Leading to Discontinuation in Part 1 | Any Grade | 18 Participants |
| Part 1: Treatment B | TRAEs Leading to Discontinuation in Part 1 | Grade 3 to 4 | 12 Participants |
| Part 1: Treatment B | TRAEs Leading to Discontinuation in Part 1 | Grade 5 | 0 Participants |