Metastatic Non-small Cell Lung Cancer
Conditions
Brief summary
This study is to assess the pharmacokinetics (PK) and safety of SC pembrolizumab formulated with berahyaluronidase alfa (MK-3475A) versus (vs) intravenous (IV) pembrolizumab (MK-3475), administered with chemotherapy in first line treatment of adult participants with metastatic non-small cell lung cancer. The primary hypotheses of this study are pembrolizumab formulated with berahyaluronidase alfa subcutaneous (SC) is noninferior to pembrolizumab IV with respect to PK parameters.
Interventions
BIOLOGICALPembrolizumab Formulated with Berahyaluronidase Alfa
Pembrolizumab (+) Berahyaluronidase alfa SC will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.
DRUGPemetrexed
Pemetrexed 500 mg/m² by IV Infusion will be administered for nonsquamous NSCLC as per the schedule specified in arm.
DRUGCisplatin
Cisplatin 75 mg/m² by IV Infusion will be administered for nonsquamous and squamous NSCLC as per the schedule specified in arm.
DRUGCarboplatin
Carboplatin AUC 5 mg/mL/min in nonsquamous and AUC 6 mg/mL/min in squamous NSCLC will be administered as per the schedule specified in arm.
DRUGPaclitaxel
Paclitaxel 200 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
DRUGNab-paclitaxel
Nab-paclitaxel 100 mg/m² by IV Infusion will be administered for squamous NSCLC as per the schedule specified in arm.
BIOLOGICALPembrolizumab
Pembrolizumab by IV Infusion will be administered for squamous and nonsquamous NSCLC as per the schedule specified in arm; participants may be eligible for second course.
DRUGFilgrastim
Filgrastim will be administered as per the schedule specified for the arm.
Pegylated filgrastim will be administered as per the schedule specified for the arm.
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
The key inclusion and
Exclusion criteria
include but are not limited to the following: Inclusion Criteria: * Has histologically or cytologically confirmed diagnosis of squamous or non-squamous Non-small Cell Lung Cancer (NSCLC) * Must provide archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated * Has a life expectancy of at least 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose | Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days) | AUC0-6 weeks was defined as a measure of pembrolizumab exposure that was calculated as the product of serum drug concentration and time from zero to 6 weeks. Blood samples were collected at pre-specified timepoints to determine AUC0-6 weeks. Per protocol, geometric mean AUC0-6 weeks value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented. |
| Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State | Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days) | Ctrough was defined as the lowest serum concentration of pembrolizumab reached at steady state. Blood samples were collected at pre-specified timepoints for the determination of Ctrough. Per protocol, geometric mean Ctrough value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and of pembrolizumab in arm 2 was presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State | Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days) | AUC0-6 weeks was defined as a measure of pembrolizumab exposure that was calculated as the product of serum drug concentration and time from zero to 6 weeks. Blood samples were collected at pre-specified timepoints to determine AUC0-6 weeks. Per protocol, geometric mean AUC0-6 weeks value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and pembrolizumab in arm 2 was presented. |
| Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State | Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days) | Cmax was defined as the maximum serum concentration of pembrolizumab reached at steady state. Blood samples were collected at pre-specified timepoints to determine Cmax. Per protocol, geometric mean Cmax value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and pembrolizumab in arm 2 was presented. |
| Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab | Predose and Postdose on Day 1 of Cycles 1 through 18 (up to approximately 28 months). Each cycle is 6 weeks. | Blood samples were collected at designated time points for the determination of the presence or absence of anti-pembrolizumab antibodies. Per protocol, the number of participants who developed anti pembrolizumab antibodies were reported. |
| Objective Response Rate (ORR) | Up to approximately 28 months | ORR was defined as the percentage of participants with 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 Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by Blinded Independent Central Review (BICR) were presented. |
| Progression-free Survival (PFS) | Up to approximately 28 months | PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by RECIST 1.1. 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. PFS as assessed by BICR were presented. |
| Overall Survival (OS) | Up to approximately 28 months | OS was defined as the time from randomization to death due to any cause. |
| Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose | Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days) | Cmax was defined as the maximum serum concentration of pembrolizumab reached after first dose. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, geometric mean Cmax value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented. |
| Number of Participants Who Experienced at Least One Adverse Event (AE) | Up to approximately 28 months | An AE was 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. The number of participants who experienced at least one AE were reported . |
| Number of Participants Who Discontinued Study Treatment Due to 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. The number of participants who discontinue study treatment due to an AE will be reported for Arms 1 and 2. |
| Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core30 (QLQ-C30) Combined Global Health Status/Quality of Life (Items 29 & 30) Scale Combined Score | Baseline and Week 24 | EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; How would you rate your overall health during the past week?) and QoL (How would you rate your overall quality of life during the past week?) are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in GHS and QoL combined score was presented. |
| Change From Baseline in Physical Functioning (EORTC-QLQ-C30 Items 1-5) Score | Baseline and Week 24 | EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score was presented. |
| Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Role Functioning Score-Items 6 and 7 | Baseline and Week 24 | EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the questions Were you limited in doing either your work or other daily activities during the past week? and Were you limited in pursuing your hobbies or other leisure time activities during the past week? will be scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicate a better level of role functioning. Change from baseline in the EORTC QLQ-C30 role functioning (Items 6-7) combined score was presented. |
| Duration of Response (DOR) | Up to approximately 28 months | For participants who demonstrated a 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, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, 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. DOR as assessed by BICR were presented. |
| Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose | Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days) | Ctrough was defined as the lowest serum concentration of pembrolizumab reached after first dose. Blood samples were collected at pre-specified timepoints for the determination of Ctrough. Per protocol, geometric mean Ctrough value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented. |
Countries
Argentina, Brazil, Chile, China, France, Guatemala, Hungary, Japan, Poland, Romania, South Africa, Spain, Taiwan, Thailand, Turkey (Türkiye), United States
Participant flow
Pre-assignment details
All randomized participants.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy Participants with treatment-naïve metastatic NSCLC receive 790 mg of Pembrolizumab Formulated With Berahyaluronidase Alfa via subcutaneous (SC) injection on Day 1 of each 6-week cycle for 18 cycles (up to approximately 108 weeks) in combination with platinum doublet chemotherapy. | 251 |
| Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy Participants with treatment-naïve metastatic NSCLC receive 400 mg pembrolizumab intravenous (IV) infusion in combination with platinum doublet chemotherapy. | 126 |
| Total | 377 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 57 | 37 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Participants Ongoing | 188 | 88 |
| Overall Study | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy | Total | Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy |
|---|---|---|---|
| Age, Continuous | 64.8 Years STANDARD_DEVIATION 8.5 | 64.8 Years STANDARD_DEVIATION 9.2 | 64.7 Years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 41 Participants | 115 Participants | 74 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 85 Participants | 262 Participants | 177 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 4 Participants | 6 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 36 Participants | 110 Participants | 74 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 10 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 3 Participants | 15 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 78 Participants | 236 Participants | 158 Participants |
| Sex: Female, Male Female | 40 Participants | 109 Participants | 69 Participants |
| Sex: Female, Male Male | 86 Participants | 268 Participants | 182 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 61 / 251 | 37 / 126 |
| other Total, other adverse events | 236 / 251 | 123 / 126 |
| serious Total, serious adverse events | 98 / 251 | 51 / 126 |
Outcome results
Primary
Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose
AUC0-6 weeks was defined as a measure of pembrolizumab exposure that was calculated as the product of serum drug concentration and time from zero to 6 weeks. Blood samples were collected at pre-specified timepoints to determine AUC0-6 weeks. Per protocol, geometric mean AUC0-6 weeks value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.
Time frame: Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)
Population: All randomized participants who received a dose in Cycle 1 with at least 1 valid postdose pharmacokinetic (PK) sample available in Cycle 1 and for whom a model-based assessment of AUC0-6 weeks could be made.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy | Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose | 1633.24 μg·day/mL | Geometric Coefficient of Variation 40.41 |
| Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy | Cycle 1: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab After the First Dose | 1437.58 μg·day/mL | Geometric Coefficient of Variation 26.23 |
p-value: <0.0000196% CI: [1.06, 1.22]Welch's t test
Primary
Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State
Ctrough was defined as the lowest serum concentration of pembrolizumab reached at steady state. Blood samples were collected at pre-specified timepoints for the determination of Ctrough. Per protocol, geometric mean Ctrough value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and of pembrolizumab in arm 2 was presented.
Time frame: Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)
Population: All randomized participants who received a dose in Cycle 1 and Cycle 3 with at least 1 valid postdose PK sample available in Cycle 1 through Cycle 3 and for whom a model-based assessment of Ctrough could be made.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy | Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State | 39.23 μg/mL | Geometric Coefficient of Variation 43.29 |
| Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy | Cycle 3: Trough Serum Concentration (Ctrough) of Pembrolizumab at Steady State | 23.49 μg/mL | Geometric Coefficient of Variation 44.23 |
p-value: <0.0000194% CI: [1.52, 1.84]Welch's t test
Secondary
Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core30 (QLQ-C30) Combined Global Health Status/Quality of Life (Items 29 & 30) Scale Combined Score
EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; How would you rate your overall health during the past week?) and QoL (How would you rate your overall quality of life during the past week?) are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in GHS and QoL combined score was presented.
Time frame: Baseline and Week 24
Secondary
Change From Baseline in Physical Functioning (EORTC-QLQ-C30 Items 1-5) Score
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score was presented.
Time frame: Baseline and Week 24
Secondary
Change From Baseline in the European Organization for the Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) Role Functioning Score-Items 6 and 7
EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the questions Were you limited in doing either your work or other daily activities during the past week? and Were you limited in pursuing your hobbies or other leisure time activities during the past week? will be scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. Higher scores indicate a better level of role functioning. Change from baseline in the EORTC QLQ-C30 role functioning (Items 6-7) combined score was presented.
Time frame: Baseline and Week 24
Secondary
Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose
Cmax was defined as the maximum serum concentration of pembrolizumab reached after first dose. Blood samples were collected at pre-specified timepoints for the determination of Cmax. Per protocol, geometric mean Cmax value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.
Time frame: Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)
Population: All randomized participants who received a dose in Cycle 1 with at least 1 valid postdose PK sample available in Cycle 1 and for whom a model-based assessment of Cmax could be made.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy | Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose | 64.88 μg/mL | Geometric Coefficient of Variation 44 |
| Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy | Cycle 1: Maximum Serum Concentration (Cmax) of Pembrolizumab After the First Dose | 129.7 μg/mL | Geometric Coefficient of Variation 20.8 |
Secondary
Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose
Ctrough was defined as the lowest serum concentration of pembrolizumab reached after first dose. Blood samples were collected at pre-specified timepoints for the determination of Ctrough. Per protocol, geometric mean Ctrough value of pembrolizumab after the first dose of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and after first dose of pembrolizumab in arm 2 was presented.
Time frame: Cycle 1: Arm 1: Day 1: Predose and Days 2, 3, 4, 5, 6, 7, 10, 15, 29, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4, 15, 29, and 42 postdose (cycle length = 42 days)
Population: All randomized participants who received a dose in Cycle 1 with at least 1 valid postdose PK sample available in Cycle 1 and for whom a model-based assessment of Ctrough could be made.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy | Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose | 19.36 μg/mL | Geometric Coefficient of Variation 52.2 |
| Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy | Cycle 1: Trough Serum Concentration (Ctrough) of Pembrolizumab After the First Dose | 12.26 μg/mL | Geometric Coefficient of Variation 50.8 |
Secondary
Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State
AUC0-6 weeks was defined as a measure of pembrolizumab exposure that was calculated as the product of serum drug concentration and time from zero to 6 weeks. Blood samples were collected at pre-specified timepoints to determine AUC0-6 weeks. Per protocol, geometric mean AUC0-6 weeks value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and pembrolizumab in arm 2 was presented.
Time frame: Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)
Population: All randomized participants who received a dose in Cycle 1 and Cycle 3 with at least 1 valid postdose PK sample available in Cycle 1 through Cycle 3 and for whom a model-based assessment of AUC0-6 weeks could be made.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy | Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State | 2798 μg·day/mL | Geometric Coefficient of Variation 35.5 |
| Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy | Cycle 3: Area Under the Curve From Time 0 to 6 Weeks (AUC0-6 Weeks) of Pembrolizumab at Steady State | 2122 μg·day/mL | Geometric Coefficient of Variation 27.8 |
Secondary
Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State
Cmax was defined as the maximum serum concentration of pembrolizumab reached at steady state. Blood samples were collected at pre-specified timepoints to determine Cmax. Per protocol, geometric mean Cmax value of pembrolizumab at steady state of pembrolizumab formulated with berahyaluronidase alfa in arm 1 and pembrolizumab in arm 2 was presented.
Time frame: Cycle 3: Arm 1: Day 1: Predose and Days 4, 10, and 42 postdose; Arm 2: Day 1: Predose and at the end of infusion, Days 4 and 42 postdose (cycle length = 42 days)
Population: All randomized participants who received a dose in Cycle 1 and Cycle 3 with at least 1 valid postdose PK sample available in Cycle 1 through Cycle 3 and for whom a model-based assessment of Cmax could be made.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Pembrolizumab Formulated With Berahyaluronidase Alfa + Platinum Doublet Chemotherapy | Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State | 98.96 μg/mL | Geometric Coefficient of Variation 36.8 |
| Arm 2: Pembrolizumab + Platinum Doublet Chemotherapy | Cycle 3: Maximum Serum Concentration (Cmax) of Pembrolizumab at Steady State | 148 μg/mL | Geometric Coefficient of Variation 21.6 |
Secondary
Duration of Response (DOR)
For participants who demonstrated a 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, DOR is defined as the time from first documented evidence of CR or PR until PD or death. Per RECIST 1.1, 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. DOR as assessed by BICR were presented.
Time frame: Up to approximately 28 months
Secondary
Number of Participants Who Discontinued Study Treatment Due to 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. The number of participants who discontinue study treatment due to an AE will be reported for Arms 1 and 2.
Time frame: Up to approximately 28 months
Secondary
Number of Participants Who Experienced at Least One Adverse Event (AE)
An AE was 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. The number of participants who experienced at least one AE were reported .
Time frame: Up to approximately 28 months
Secondary
Number of Participants Who Test Positive for Anti-Drug Antibodies (ADAs) for Pembrolizumab
Blood samples were collected at designated time points for the determination of the presence or absence of anti-pembrolizumab antibodies. Per protocol, the number of participants who developed anti pembrolizumab antibodies were reported.
Time frame: Predose and Postdose on Day 1 of Cycles 1 through 18 (up to approximately 28 months). Each cycle is 6 weeks.
Secondary
Objective Response Rate (ORR)
ORR was defined as the percentage of participants with 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 Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experienced CR or PR as assessed by Blinded Independent Central Review (BICR) were presented.
Time frame: Up to approximately 28 months
Secondary
Overall Survival (OS)
OS was defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 28 months
Secondary
Progression-free Survival (PFS)
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by RECIST 1.1. 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. PFS as assessed by BICR were presented.
Time frame: Up to approximately 28 months