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Study of Pembrolizumab (MK-3475) Subcutaneous (SC) Versus Pembrolizumab Intravenous (IV) Administered With Platinum Doublet Chemotherapy in Participants With Metastatic Squamous or Nonsquamous Non-Small Cell Lung Cancer (NSCLC) (MK-3475-A86)

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ClinicalTrials.gov Identifier: NCT04956692
Recruitment Status : Active, not recruiting
First Posted : July 9, 2021
Results First Posted : May 17, 2024
Last Update Posted : May 17, 2024
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Non-Small Cell Lung Cancer
Interventions Biological: Pembrolizumab SC
Biological: Pembrolizumab IV
Drug: Paclitaxel
Drug: Nab-Paclitaxel
Drug: Carboplatin
Drug: Cisplatin
Drug: Pemetrexed
Enrollment 531
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 358 173
Treated 356 172
Completed 0 0
Not Completed 358 173
Reason Not Completed
Death             115             47
Lost to Follow-up             0             1
Withdrawal by Parent/Guardian             2             0
Withdrawal by Subject             5             2
Ongoing in Study             236             123
Arm/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 358 173 531
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 358 participants 173 participants 531 participants
64.1  (8.6) 65.6  (9.2) 64.6  (8.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 358 participants 173 participants 531 participants
Female
101
  28.2%
47
  27.2%
148
  27.9%
Male
257
  71.8%
126
  72.8%
383
  72.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 358 participants 173 participants 531 participants
Hispanic or Latino
50
  14.0%
27
  15.6%
77
  14.5%
Not Hispanic or Latino
307
  85.8%
146
  84.4%
453
  85.3%
Unknown or Not Reported
1
   0.3%
0
   0.0%
1
   0.2%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 358 participants 173 participants 531 participants
American Indian or Alaska Native
6
   1.7%
3
   1.7%
9
   1.7%
Asian
72
  20.1%
32
  18.5%
104
  19.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
8
   2.2%
3
   1.7%
11
   2.1%
White
232
  64.8%
113
  65.3%
345
  65.0%
More than one race
24
   6.7%
14
   8.1%
38
   7.2%
Unknown or Not Reported
16
   4.5%
8
   4.6%
24
   4.5%
1.Primary Outcome
Title Cycle 1 Area Under The Curve From 0-3 Weeks (AUC 0-3wks) of Pembrolizumab
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 355 170
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr*µg/mL
471.33
(452.22 to 491.26)
454.96
(438.54 to 471.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy, Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments The non-inferiority margin with respect to the geometric means ratio (GMR) was 0.8
Statistical Test of Hypothesis P-Value <0.0001
Comments The one-sided p-value non-inferiority boundary is 0.02
Method t-test, 1 sided
Comments Welch's unequal variances t-test. The null hypothesis was that GMR≤0.8.
Method of Estimation Estimation Parameter Geometric Mean Ratio (GMR)
Estimated Value 1.04
Confidence Interval (2-Sided) 96%
0.98 to 1.10
Estimation Comments Numerator Arm A/Denominator Arm B
2.Primary Outcome
Title Cycle 6 Model-Based Minimal Concentration (Ctrough) of Pembrolizumab
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 240 93
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
55.93
(53.05 to 58.96)
30.25
(27.93 to 32.77)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy, Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments The non-inferiority margin with respect to the geometric means ratio (GMR) was 0.8
Statistical Test of Hypothesis P-Value <0.0001
Comments The one-sided p-value non-inferiority boundary is 0.03
Method t-test, 1 sided
Comments Welch's unequal variances t-test. The null hypothesis was that GMR≤0.8.
Method of Estimation Estimation Parameter Geometric Mean Ratio (GMR)
Estimated Value 1.85
Confidence Interval (2-Sided) 94%
1.69 to 2.03
Estimation Comments Numerator Arm A/Denominator Arm B
3.Secondary Outcome
Title Objective Response (OR) Per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
Hide Description 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
Outcome Measure Data Not Reported
4.Secondary Outcome
Title Cycle 1 Observed Ctrough of Pembrolizumab
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all randomized participants with at least 1 postdose sample in cycle 1.
Arm/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 263 134
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
18.36
(17.19 to 19.61)
11.16
(10.49 to 11.88)
5.Secondary Outcome
Title Cycle 1 Maximum Concentration (Cmax) of Pembrolizumab
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all randomized participants with at least 1 postdose sample in cycle 1.
Arm/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 355 170
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
25.2
(23.8 to 26.6)
58.3
(55.7 to 61.0)
6.Secondary Outcome
Title Cycle 6 AUC 0-3wks of Pembrolizumab
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 240 93
Geometric Mean (95% Confidence Interval)
Unit of Measure: hr*µg/mL
1403.8
(1342.0 to 1468.5)
952.9
(896.4 to 1013.0)
7.Secondary Outcome
Title Cycle 6 Cmax of Pembrolizumab
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all randomized participants with at least 1 postdose sample in cycle 6.
Arm/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 240 93
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
65.6
(62.2 to 69.0)
85.6
(80.1 to 91.4)
8.Secondary Outcome
Title Cycle 6 Observed Ctrough of Pembrolizumab
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis population includes all randomized participants with at least 1 postdose sample in cycle 6.
Arm/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 61 23
Geometric Mean (95% Confidence Interval)
Unit of Measure: µg/mL
57.17
(52.23 to 62.58)
33.19
(29.53 to 37.30)
9.Secondary Outcome
Title Number of Participants Who Experienced an Adverse Event (AE)
Hide Description 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
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Number of Participants Who Discontinued Study Treatment Due to an AE
Hide Description 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
Outcome Measure Data Not Reported
11.Secondary Outcome
Title Progression-Free Survival (PFS) Per RECIST 1.1 as Assessed by BICR
Hide Description 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
Outcome Measure Data Not Reported
12.Secondary Outcome
Title Overall Survival (OS)
Hide Description OS is defined as the time from randomization to death due to any cause.
Time Frame Up to approximately 5 years
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
Hide Description 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
Outcome Measure Data Not Reported
14.Secondary Outcome
Title Anti-Drug Antibodies (ADAs) Incidence After Administration of Pembrolizumab
Hide Description 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
Outcome Measure Data Not Reported
Time Frame Up to approximately 19 months
Adverse Event Reporting Description All-Cause Mortality includes all participants who enrolled. Adverse Events include all participants who received ≥1 dose of study drug.
 
Arm/Group Title Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   118/358 (32.96%)      48/173 (27.75%)    
Hide Serious Adverse Events
Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   132/356 (37.08%)      62/172 (36.05%)    
Blood and lymphatic system disorders     
Anaemia  1  18/356 (5.06%)  19 2/172 (1.16%)  2
Anaemia of chronic disease  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Febrile neutropenia  1  9/356 (2.53%)  9 5/172 (2.91%)  5
Leukocytosis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Neutropenia  1  7/356 (1.97%)  8 3/172 (1.74%)  3
Thrombocytopenia  1  5/356 (1.40%)  5 3/172 (1.74%)  4
Cardiac disorders     
Acute myocardial infarction  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Arrhythmia supraventricular  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Atrial fibrillation  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Cardiac arrest  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Cardiac failure acute  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Myocardial infarction  1  0/356 (0.00%)  0 2/172 (1.16%)  2
Pericardial effusion  1  1/356 (0.28%)  2 0/172 (0.00%)  0
Supraventricular extrasystoles  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Supraventricular tachyarrhythmia  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Congenital, familial and genetic disorders     
Aplasia  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Ear and labyrinth disorders     
Vertigo  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Endocrine disorders     
Adrenal insufficiency  1  1/356 (0.28%)  1 1/172 (0.58%)  1
Hypothyroidism  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Eye disorders     
Macular hole  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Gastrointestinal disorders     
Colitis  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Diarrhoea  1  3/356 (0.84%)  3 1/172 (0.58%)  1
Gastrointestinal haemorrhage  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Haematemesis  1  1/356 (0.28%)  1 1/172 (0.58%)  1
Ileus  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Ileus paralytic  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Incarcerated inguinal hernia  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Nausea  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Neutropenic colitis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Oesophageal fistula  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Oesophageal haemorrhage  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pancreatitis  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Stomatitis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Vomiting  1  2/356 (0.56%)  2 0/172 (0.00%)  0
General disorders     
Asthenia  1  5/356 (1.40%)  5 3/172 (1.74%)  3
Death  1  3/356 (0.84%)  3 0/172 (0.00%)  0
Face oedema  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Fatigue  1  0/356 (0.00%)  0 3/172 (1.74%)  3
Generalised oedema  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Hypothermia  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Injection site exfoliation  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Non-cardiac chest pain  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Oedema peripheral  1  0/356 (0.00%)  0 2/172 (1.16%)  2
Pain  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Peripheral swelling  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Sudden death  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Hepatobiliary disorders     
Cholecystitis  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Cholecystitis acute  1  1/356 (0.28%)  1 1/172 (0.58%)  2
Immune-mediated hepatitis  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Infections and infestations     
Appendicitis  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Bronchitis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
COVID-19  1  5/356 (1.40%)  5 3/172 (1.74%)  3
COVID-19 pneumonia  1  5/356 (1.40%)  5 1/172 (0.58%)  1
Cellulitis  1  1/356 (0.28%)  1 1/172 (0.58%)  1
Diverticulitis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Gastroenteritis  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Gastrointestinal infection  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Haemophilus infection  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Herpes zoster  1  2/356 (0.56%)  2 2/172 (1.16%)  2
Infected fistula  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Infectious pleural effusion  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Laryngitis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Neutropenic sepsis  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Peritonsillar abscess  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pleural infection  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pneumocystis jirovecii pneumonia  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pneumonia  1  11/356 (3.09%)  11 10/172 (5.81%)  11
Pneumonia aspiration  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Pneumonia bacterial  1  1/356 (0.28%)  1 1/172 (0.58%)  1
Pulmonary sepsis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pyopneumothorax  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Sepsis  1  5/356 (1.40%)  5 1/172 (0.58%)  1
Septic shock  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Staphylococcal infection  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Systemic infection  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Urinary tract infection  1  0/356 (0.00%)  0 2/172 (1.16%)  2
Injury, poisoning and procedural complications     
Alcohol poisoning  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Concussion  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Craniocerebral injury  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Femur fracture  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Hip fracture  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Joint injury  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Toxicity to various agents  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Investigations     
Alanine aminotransferase increased  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Aspartate aminotransferase increased  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Blood bilirubin increased  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Blood creatinine increased  1  1/356 (0.28%)  1 0/172 (0.00%)  0
C-reactive protein increased  1  1/356 (0.28%)  1 0/172 (0.00%)  0
White blood cell count decreased  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Metabolism and nutrition disorders     
Decreased appetite  1  2/356 (0.56%)  2 1/172 (0.58%)  1
Dehydration  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Diabetes mellitus  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Diabetic ketoacidosis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Hypercalcaemia  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Hyponatraemia  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Hypophosphataemia  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Musculoskeletal and connective tissue disorders     
Back pain  1  1/356 (0.28%)  1 1/172 (0.58%)  1
Connective tissue inflammation  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Myositis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pain in extremity  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Polymyalgia rheumatica  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Soft tissue haemorrhage  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Malignant pleural effusion  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Plasma cell myeloma  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Nervous system disorders     
Carotid artery stenosis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Cerebral artery embolism  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Cerebrovascular accident  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Ischaemic stroke  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Metabolic encephalopathy  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Myasthenia gravis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Seizure  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Transient ischaemic attack  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Psychiatric disorders     
Confusional state  1  1/356 (0.28%)  1 1/172 (0.58%)  2
Delusional disorder, unspecified type  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Renal and urinary disorders     
Calculus bladder  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Immune-mediated nephritis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Renal impairment  1  2/356 (0.56%)  2 0/172 (0.00%)  0
Tubulointerstitial nephritis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  1/356 (0.28%)  2 4/172 (2.33%)  6
Dyspnoea  1  1/356 (0.28%)  1 2/172 (1.16%)  3
Epistaxis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Haemoptysis  1  2/356 (0.56%)  2 1/172 (0.58%)  1
Haemothorax  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pleural effusion  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pleurisy  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pneumonitis  1  6/356 (1.69%)  6 6/172 (3.49%)  6
Pneumothorax  1  2/356 (0.56%)  2 1/172 (0.58%)  1
Pulmonary artery thrombosis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Pulmonary embolism  1  4/356 (1.12%)  4 1/172 (0.58%)  1
Pulmonary haemorrhage  1  2/356 (0.56%)  2 1/172 (0.58%)  1
Pulmonary oedema  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Respiratory failure  1  1/356 (0.28%)  1 3/172 (1.74%)  3
Skin and subcutaneous tissue disorders     
Dermatitis  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Rash  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Rash maculo-papular  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Stevens-Johnson syndrome  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Vascular disorders     
Arterial thrombosis  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Deep vein thrombosis  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Embolism  1  1/356 (0.28%)  1 0/172 (0.00%)  0
Hypotension  1  1/356 (0.28%)  1 1/172 (0.58%)  1
Hypovolaemic shock  1  0/356 (0.00%)  0 1/172 (0.58%)  1
Venous thrombosis limb  1  1/356 (0.28%)  1 0/172 (0.00%)  0
1
Term from vocabulary, MedDRA 26.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A: Pembrolizumab SC + Platinum Doublet Chemotherapy Arm B: Pembrolizumab IV + Platinum Doublet Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   331/356 (92.98%)      160/172 (93.02%)    
Blood and lymphatic system disorders     
Anaemia  1  188/356 (52.81%)  237 100/172 (58.14%)  118
Neutropenia  1  116/356 (32.58%)  218 52/172 (30.23%)  107
Thrombocytopenia  1  83/356 (23.31%)  137 40/172 (23.26%)  62
Endocrine disorders     
Hyperthyroidism  1  24/356 (6.74%)  26 7/172 (4.07%)  8
Hypothyroidism  1  25/356 (7.02%)  27 8/172 (4.65%)  8
Gastrointestinal disorders     
Constipation  1  57/356 (16.01%)  70 27/172 (15.70%)  33
Diarrhoea  1  59/356 (16.57%)  77 23/172 (13.37%)  28
Nausea  1  98/356 (27.53%)  141 48/172 (27.91%)  64
Stomatitis  1  22/356 (6.18%)  24 5/172 (2.91%)  5
Vomiting  1  32/356 (8.99%)  39 12/172 (6.98%)  17
General disorders     
Asthenia  1  46/356 (12.92%)  56 31/172 (18.02%)  38
Fatigue  1  41/356 (11.52%)  46 14/172 (8.14%)  15
Oedema peripheral  1  24/356 (6.74%)  25 13/172 (7.56%)  13
Pyrexia  1  24/356 (6.74%)  27 8/172 (4.65%)  8
Infections and infestations     
COVID-19  1  24/356 (6.74%)  24 11/172 (6.40%)  11
Investigations     
Alanine aminotransferase increased  1  46/356 (12.92%)  60 26/172 (15.12%)  37
Aspartate aminotransferase increased  1  46/356 (12.92%)  63 29/172 (16.86%)  40
Blood alkaline phosphatase increased  1  18/356 (5.06%)  26 12/172 (6.98%)  14
Blood creatinine increased  1  34/356 (9.55%)  44 18/172 (10.47%)  27
Blood lactate dehydrogenase increased  1  22/356 (6.18%)  22 10/172 (5.81%)  11
Lymphocyte count decreased  1  19/356 (5.34%)  26 10/172 (5.81%)  15
White blood cell count decreased  1  50/356 (14.04%)  81 26/172 (15.12%)  41
Metabolism and nutrition disorders     
Decreased appetite  1  60/356 (16.85%)  74 25/172 (14.53%)  27
Hyperglycaemia  1  24/356 (6.74%)  36 10/172 (5.81%)  12
Hypoalbuminaemia  1  19/356 (5.34%)  20 12/172 (6.98%)  13
Hypocalcaemia  1  17/356 (4.78%)  19 9/172 (5.23%)  9
Hypokalaemia  1  18/356 (5.06%)  26 6/172 (3.49%)  8
Hyponatraemia  1  15/356 (4.21%)  16 12/172 (6.98%)  14
Musculoskeletal and connective tissue disorders     
Arthralgia  1  31/356 (8.71%)  37 11/172 (6.40%)  19
Nervous system disorders     
Dizziness  1  17/356 (4.78%)  18 15/172 (8.72%)  17
Headache  1  20/356 (5.62%)  20 13/172 (7.56%)  15
Neuropathy peripheral  1  19/356 (5.34%)  21 8/172 (4.65%)  8
Psychiatric disorders     
Insomnia  1  22/356 (6.18%)  23 8/172 (4.65%)  9
Respiratory, thoracic and mediastinal disorders     
Cough  1  19/356 (5.34%)  21 8/172 (4.65%)  13
Dyspnoea  1  20/356 (5.62%)  22 12/172 (6.98%)  13
Hiccups  1  20/356 (5.62%)  21 4/172 (2.33%)  4
Skin and subcutaneous tissue disorders     
Alopecia  1  47/356 (13.20%)  47 23/172 (13.37%)  23
Pruritus  1  24/356 (6.74%)  27 9/172 (5.23%)  9
Rash  1  25/356 (7.02%)  28 15/172 (8.72%)  19
1
Term from vocabulary, MedDRA 26.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT04956692    
Other Study ID Numbers: 3475-A86
MK-3475-A86 ( Other Identifier: Merck )
jRCT2021210032 ( Registry Identifier: jRCT (Japan Registry of Clinical Trials) )
2020-002729-27 ( EudraCT Number )
First Submitted: July 6, 2021
First Posted: July 9, 2021
Results First Submitted: March 27, 2024
Results First Posted: May 17, 2024
Last Update Posted: May 17, 2024