Non-Small Cell Lung Cancer
Conditions
Keywords
Programmed Cell Death 1 (PD1, PD-1), Programmed Cell Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death-Ligand 2 (PDL2, PD-L2)
Brief summary
The purpose of this study is to evaluate pembrolizumab (MK-3475) subcutaneous (SC) administration as the first-line therapy in the treatment of metastatic squamous and nonsquamous NSCLC by assessing the pharmacokinetics (PK), safety, and efficacy of pembrolizumab SC injection in combination with standard-of-care chemotherapy. The primary hypothesis of the study is Pembrolizumab SC is noninferior to pembrolizumab intravenous (IV) for Cycle 1 Area Under Curve (AUC) and Cycle 6 minimal concentration (Ctrough) at steady state. Participants who discontinue study treatment after receiving the first course of 35 administrations of pembrolizumab (approximately up to 2 years) for reasons other than disease progression or intolerability, may be eligible for a second course of pembrolizumab for up to approximately 1 additional year if they have experienced radiographic disease progression per RECIST 1.1 as assessed by BICR after stopping first course treatment.
Interventions
BIOLOGICALPembrolizumab SC
SC injection
BIOLOGICALPembrolizumab IV
IV injection
DRUGPaclitaxel
IV injection
DRUGNab-Paclitaxel
IV infusion
DRUGCarboplatin
IV infusion
DRUGCisplatin
IV infusion
DRUGPemetrexed
IV infusion
Sponsors
Merck Sharp & Dohme LLC
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
* Has pathologically (histologically or cytologically) confirmed diagnosis of squamous or nonsquamous non-small cell lung cancer (NSCLC) * Has Stage IV (T any, N any, M1a, M1b, or M1c - American Joint Committee on Cancer 8th Edition) squamous or nonsquamous NSCLC * Has confirmation that epidermal growth factor receptor (EGFR), Anaplastic lymphoma kinase (ALK), or ROS Proto-Oncogene 1, Receptor Tyrosine Kinase (ROS1)-directed therapy is not indicated in nonsquamous NSCLC as well as mixed nonsquamous/squamous NSCLC. Participants with purely squamous NSCLC do not require testing * Has not received prior systemic treatment for their metastatic NSCLC. Participants who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease * Has an Eastern Cooperative Oncology Group (ECOG) performance score (PS) of 0 or 1 * Male participants are eligible to participate if they agree to use contraception as per protocol unless confirmed to be azoospermic * A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) or is a WOCBP who agrees of using a contraceptive method per protocol * Has measurable disease per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by the local site investigator/radiology * Submit an archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated for PD-L1 status determination prior to randomization * Has adequate organ function
Exclusion criteria
* Has a known additional malignancy that is progressing or has required active treatment within the past 3 years * Has known central nervous system (ie, brain and/or spinal cord) metastases and/or carcinomatous meningitis. Participants with treated brain metastases may participate only if they satisfy all of the following: a) Have no evidence of new or enlarging brain metastases confirmed by post-treatment repeat brain imaging performed at least 4 weeks after pretreatment brain imaging, and b) Are neurologically stable without the need for steroids for at least 14 days before first dose of trial treatment as per local site assessment * Has severe hypersensitivity to study intervention and/or any of its excipients * Has an active autoimmune disease that has required systemic treatment in past 2 years * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Has an active infection requiring systemic therapy * Has a known history of human immunodeficiency virus (HIV) infection and/or Hepatitis B infection or known active Hepatitis C infection * Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study * Has symptomatic ascites or pleural effusion. A participant who is clinically stable after treatment for these conditions is eligible * Before the first dose of study intervention: a) Has received prior systemic cytotoxic chemotherapy for metastatic NSCLC b) Has received antineoplastic biological therapy for metastatic NSCLC c) Has had major surgery (\<3 weeks prior to first dose) d) Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti-programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor * Received radiation therapy to the lung that is \>30 Gray within 6 months of the first dose of study intervention * Is expected to require any other form of antineoplastic therapy while on study * For participants with nonsquamous histology: Is unable to interrupt aspirin or other Non-steroidal anti-inflammatory drugs (NSAIDs), other than an aspirin dose ≤1.3 g/day, for a 5-day period * For participants with nonsquamous histology: Is unable or unwilling to take folic acid or vitamin B12 supplementation * Has received prior radiotherapy within 2 weeks of start of study intervention or have had a history of radiation pneumonitis. Participants must have recovered from all radiation-related toxicities and not require corticosteroids. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease * Has received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention * Has had an allogenic tissue/solid organ transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cycle 1 Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab | Cycle 1: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 2: predose day 1. Each cycle is 21 days. | Cycle 1 AUC0-3wks is defined as the area under the concentration-time curve for pembrolizumab in plasma over a 3-week dosing interval in Cycle 1. Each cycle is 21 days. |
| Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab | Cycle 6: predose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days. | Cycle 6 model-based Ctrough is defined as the lowest concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 6, as predicted by the pharmacokinetic (PK) model based on historical intravenous pembrolizumab PK data. Each cycle is 21 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cycle 1 Maximum Concentration (Cmax) of Pembrolizumab | Cycle 1: predose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 2: predose day 1. Each cycle is 21 days. | Cycle 1 Cmax is defined as the observed peak concentration of pembrolizumab in plasma over the dosing interval in Cycle 1. Each cycle is 21 days. |
| Cycle 6 AUC 0-3wks of Pembrolizumab | Cycle 6: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days. | Cycle 6 AUC0-3wks is defined as the area under the concentration-time curve for pembrolizumab in plasma over a 3-week dosing interval in Cycle 6. Each cycle is 21 days. |
| Cycle 6 Cmax of Pembrolizumab | Cycle 6: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days. | Cmax in Cycle 6 is defined as the observed peak concentration of pembrolizumab in plasma over the dosing interval in Cycle 6. Each cycle is 21 days. |
| Cycle 6 Observed Ctrough of Pembrolizumab | Predose Cycle 7 day 1. Each cycle is 21 days. | Cycle 6 observed Ctrough is defined as the lowest observed concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 6. Each cycle is 21 days. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to approximately 28 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported. |
| Objective Response (OR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) | Up to approximately 5 years | The OR rate is defined as the percentage of participants who achieve a confirmed complete response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR. |
| Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR | Up to approximately 5 years | PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. |
| Overall Survival (OS) | Up to approximately 5 years | OS is defined as the time from randomization to death due to any cause. |
| Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR | Up to approximately 5 years | For participants who show confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. |
| Anti-Drug Antibodies (ADAs) Incidence After Administration of Pembrolizumab | Up to approximately 26 months | ADA incidence will be assessed by analyzing the development of ADAs following administration of pembrolizumab SC and pembrolizumab IV. |
| Number of Participants Who Discontinued Study Treatment Due to an AE | Up to approximately 25 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants who discontinue study treatment due to an AE will be presented. |
| Cycle 1 Observed Ctrough of Pembrolizumab | Predose Cycle 2 day 1. Each cycle is 21 days. | Cycle 1 observed Ctrough is defined as the lowest observed concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 1. Each cycle is 21 days. |
Countries
Brazil, France, Guatemala, Hungary, Japan, Peru, Poland, Romania, Russia, South Africa, South Korea, Spain, Taiwan, Turkey (Türkiye), Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Participants receive pembrolizumab subcutaneous (SC) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \
2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for squamous non-small cell lung cancer (NSCLC); PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for non-squamous NSCLC. | 358 |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy Participants receive pembrolizumab intravenous (IV) administration on Day 1 of each cycle (cycle length = 3 weeks) for up to 35 cycles (up to \
2 years) PLUS paclitaxel IV (on Day 1 of each cycle) OR nab-paclitaxel IV (on Days 1, 8, and 15 of each cycle) and carboplatin IV (on Day 1 of each cycle) for 4 cycles for squamous non-small cell lung cancer (NSCLC); PLUS carboplatin IV (on Day 1 of each cycle) Or cisplatin IV (on Day 1 of each cycle) for 4 cycles and pemetrexed IV (on Day 1 of each cycle) until progression, intolerable adverse events, or participant/physician decision for non-squamous NSCLC. | 173 |
| Total | 531 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 115 | 47 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Ongoing in Study | 236 | 123 |
| Overall Study | Withdrawal by Parent/Guardian | 2 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 2 |
Baseline characteristics
| Characteristic | Total | Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy |
|---|---|---|---|
| Age, Continuous | 64.6 Years STANDARD_DEVIATION 8.8 | 65.6 Years STANDARD_DEVIATION 9.2 | 64.1 Years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 77 Participants | 27 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 453 Participants | 146 Participants | 307 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 9 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) Asian | 104 Participants | 32 Participants | 72 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 3 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 38 Participants | 14 Participants | 24 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 24 Participants | 8 Participants | 16 Participants |
| Race (NIH/OMB) White | 345 Participants | 113 Participants | 232 Participants |
| Sex: Female, Male Female | 148 Participants | 47 Participants | 101 Participants |
| Sex: Female, Male Male | 383 Participants | 126 Participants | 257 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 118 / 358 | 48 / 173 |
| other Total, other adverse events | 331 / 356 | 160 / 172 |
| serious Total, serious adverse events | 132 / 356 | 62 / 172 |
Outcome results
Primary
Cycle 1 Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab
Cycle 1 AUC0-3wks is defined as the area under the concentration-time curve for pembrolizumab in plasma over a 3-week dosing interval in Cycle 1. Each cycle is 21 days.
Time frame: Cycle 1: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 2: predose day 1. Each cycle is 21 days.
Population: The analysis population includes all randomized participants with at least 1 postdose sample in cycle 1, and for whom a model-based assessment could be done.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy | Cycle 1 Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab | 471.33 hr*µg/mL |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Cycle 1 Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab | 454.96 hr*µg/mL |
p-value: <0.000196% CI: [0.98, 1.1]t-test, 1 sided
Primary
Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab
Cycle 6 model-based Ctrough is defined as the lowest concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 6, as predicted by the pharmacokinetic (PK) model based on historical intravenous pembrolizumab PK data. Each cycle is 21 days.
Time frame: Cycle 6: predose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.
Population: The analysis population includes all randomized participants with at least 1 postdose sample in cycle 1, and for whom a model-based assessment could be done.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy | Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab | 55.93 µg/mL |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab | 30.25 µg/mL |
p-value: <0.000194% CI: [1.69, 2.03]t-test, 1 sided
Secondary
Anti-Drug Antibodies (ADAs) Incidence After Administration of Pembrolizumab
ADA incidence will be assessed by analyzing the development of ADAs following administration of pembrolizumab SC and pembrolizumab IV.
Time frame: Up to approximately 26 months
Secondary
Cycle 1 Maximum Concentration (Cmax) of Pembrolizumab
Cycle 1 Cmax is defined as the observed peak concentration of pembrolizumab in plasma over the dosing interval in Cycle 1. Each cycle is 21 days.
Time frame: Cycle 1: predose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 2: predose day 1. Each cycle is 21 days.
Population: The analysis population includes all randomized participants with at least 1 postdose sample in cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy | Cycle 1 Maximum Concentration (Cmax) of Pembrolizumab | 25.2 µg/mL |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Cycle 1 Maximum Concentration (Cmax) of Pembrolizumab | 58.3 µg/mL |
Secondary
Cycle 1 Observed Ctrough of Pembrolizumab
Cycle 1 observed Ctrough is defined as the lowest observed concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 1. Each cycle is 21 days.
Time frame: Predose Cycle 2 day 1. Each cycle is 21 days.
Population: The analysis population includes all randomized participants with at least 1 postdose sample in cycle 1.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy | Cycle 1 Observed Ctrough of Pembrolizumab | 18.36 µg/mL |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Cycle 1 Observed Ctrough of Pembrolizumab | 11.16 µg/mL |
Secondary
Cycle 6 AUC 0-3wks of Pembrolizumab
Cycle 6 AUC0-3wks is defined as the area under the concentration-time curve for pembrolizumab in plasma over a 3-week dosing interval in Cycle 6. Each cycle is 21 days.
Time frame: Cycle 6: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.
Population: The analysis population includes all randomized participants with at least 1 postdose sample in cycle 6, and for whom a model-based assessment could be done.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy | Cycle 6 AUC 0-3wks of Pembrolizumab | 1403.8 hr*µg/mL |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Cycle 6 AUC 0-3wks of Pembrolizumab | 952.9 hr*µg/mL |
Secondary
Cycle 6 Cmax of Pembrolizumab
Cmax in Cycle 6 is defined as the observed peak concentration of pembrolizumab in plasma over the dosing interval in Cycle 6. Each cycle is 21 days.
Time frame: Cycle 6: predose and postdose day 1; days 2, 3, 4, 5, 6, 7, 10, and 15. Cycle 7: predose day 1. Each cycle is 21 days.
Population: The analysis population includes all randomized participants with at least 1 postdose sample in cycle 6.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy | Cycle 6 Cmax of Pembrolizumab | 65.6 µg/mL |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Cycle 6 Cmax of Pembrolizumab | 85.6 µg/mL |
Secondary
Cycle 6 Observed Ctrough of Pembrolizumab
Cycle 6 observed Ctrough is defined as the lowest observed concentration of pembrolizumab in plasma at the end of the dosing interval in Cycle 6. Each cycle is 21 days.
Time frame: Predose Cycle 7 day 1. Each cycle is 21 days.
Population: The analysis population includes all randomized participants with at least 1 postdose sample in cycle 6.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy | Cycle 6 Observed Ctrough of Pembrolizumab | 57.17 µg/mL |
| Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy | Cycle 6 Observed Ctrough of Pembrolizumab | 33.19 µg/mL |
Secondary
Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
For participants who show confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression (PD) per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD.
Time frame: Up to approximately 5 years
Secondary
Number of Participants Who Discontinued Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study intervention. The number of participants who discontinue study treatment due to an AE will be presented.
Time frame: Up to approximately 25 months
Secondary
Number of Participants Who Experienced an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.
Time frame: Up to approximately 28 months
Secondary
Objective Response (OR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
The OR rate is defined as the percentage of participants who achieve a confirmed complete response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 as assessed by BICR.
Time frame: Up to approximately 5 years
Secondary
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 5 years
Secondary
Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
PFS is defined as the time from randomization to the first documented PD per RECIST 1.1 by BICR or death due to any cause, whichever occurs first. PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD.
Time frame: Up to approximately 5 years