A Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in Adults With First Line Metastatic Squamous Non-small Cell Lung Cancer (MK-3475-407/KEYNOTE-407)

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ClinicalTrials.gov Identifier: NCT02775435

Recruitment Status : Completed

First Posted : May 17, 2016

Results First Posted : April 10, 2019

Last Update Posted : October 6, 2023

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Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme LLC

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition	Non-small Cell Lung Cancer
Interventions	Biological: Pembrolizumab Drug: Paclitaxel Drug: Nab-paclitaxel Drug: Carboplatin Drug: Saline placebo for pembrolizumab
Enrollment	559

Participant Flow

Recruitment Details	Interim analysis data cutoff date: 03-Apr-2018. Of the 559 randomized participants, 193 were ongoing and 75 participants randomized to chemotherapy had switched to receiving protocol-specified pembrolizumab (MK-3475). Interim results are for randomized treatment only.
Pre-assignment Details


Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy
Arm/Group Description	Participants received pembrolizumab...	Participants received normal saline...
Arm/Group Description	Participants received pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin Area Under Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Period Title: Overall Study
Started	278	281
Treated	278	280
Switched to Pembrolizumab+Chemotherapy	0	75
Completed	0	0
Not Completed	278	281
Reason Not Completed
Adverse Event	48	25
Lost to Follow-up	0	2
Physician Decision	5	6
Withdrawal by Subject	5	9
Progressive Disease	86	140
Clinical Progression	13	26
Ongoing in Study	121	72
Not Treated	0	1

Baseline Characteristics

Arm/Group Title		Pembrolizumab + Chemotherapy	Chemotherapy	Total
Arm/Group Description		Participants received pembrolizumab...	Participants received normal saline...	Total of all reporting groups
Arm/Group Description		Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Total of all reporting groups
Overall Number of Baseline Participants		278	281	559
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	278 participants	281 participants	559 participants
		65.0 (8.8)	64.8 (8.7)	64.9 (8.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	278 participants	281 participants	559 participants
	Female	58 20.9%	46 16.4%	104 18.6%
	Male	220 79.1%	235 83.6%	455 81.4%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	278 participants	281 participants	559 participants
	American Indian or Alaska Native	0 0.0%	2 0.7%	2 0.4%
	Asian	56 20.1%	52 18.5%	108 19.3%
	Native Hawaiian or Other Pacific Islander	1 0.4%	0 0.0%	1 0.2%
	Black or African American	3 1.1%	4 1.4%	7 1.3%
	White	216 77.7%	214 76.2%	430 76.9%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	2 0.7%	9 3.2%	11 2.0%
Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Level: Tumor Proportion Score (TPS) ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	278 participants	281 participants	559 participants
	TPS <1%	95 34.2%	99 35.2%	194 34.7%
	TPS ≥1%	176 63.3%	177 63.0%	353 63.1%
	Unknown	7 2.5%	5 1.8%	12 2.1%
		[1] Measure Description: Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Participants with a TPS ≥1% were classified as PD-L1 positive and participants with a TPS <1% were classified as not PD-L1 positive.
Taxane Chemotherapy ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	278 participants	281 participants	559 participants
	+Paclitaxel	169 60.8%	167 59.4%	336 60.1%
	+Nab-paclitaxel	109 39.2%	114 40.6%	223 39.9%
		[1] Measure Description: Participants were classified according to their taxane chemotherapy regimen: paclitaxel or nab-paclitaxel.
Geographic Region ^[1] Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	278 participants	281 participants	559 participants
	East Asia	54 19.4%	52 18.5%	106 19.0%
	Non-East Asia	224 80.6%	229 81.5%	453 81.0%
		[1] Measure Description: Participants were classified according to their geographic region: East Asia vs. non-East Asia.

Outcome Measures

1.Primary Outcome


Title	Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description	PFS was defined as the time from randomization to the first documented...
Description	PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. Note: The appearance of ≥1 new lesions was also considered PD. PFS as assessed by blinded independent central review per RECIST 1.1 is presented.
Time Frame	Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

Outcome Measure Data

Analysis Population Description

The Intent-To-Treat population consisted of all randomized participants, regardless of whether or not they received study treatment. Participants were included in the treatment arm to which they were randomized.


Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy
Arm/Group Description:	Participants received pembrolizumab...	Participants received normal saline...
Arm/Group Description:	Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed	278	281
Median (95% Confidence Interval) Unit of Measure: Months
	6.4 (6.2 to 8.3)	4.8 (4.2 to 5.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab + Chemotherapy, Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Treatment as a covariate stratified by programmed cell death-ligand 1 (PD-L1) status (Tumor Proportion Score [TPS] ≥1% vs. <1%), taxane chemotherapy (paclitaxel vs. nab-paclitaxel) & geographic region (East Asia vs. non-East Asia)
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.56
	Confidence Interval	(2-Sided) 95% 0.45 to 0.70
	Estimation Comments	[Not Specified]

2.Primary Outcome


Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death due to any caus...
Description	OS was defined as the time from randomization to death due to any cause. OS is presented.
Time Frame	Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy
Arm/Group Description:	Participants received pembrolizumab...	Participants received normal saline...
Arm/Group Description:	Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed	278	281
Median (95% Confidence Interval) Unit of Measure: Months
	15.9 ^[1] (13.2 to NA)	11.3 (9.5 to 14.8)

[1]

NA=OS upper limit not reached

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab + Chemotherapy, Chemotherapy
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.0008
	Comments	Treatment as a covariate stratified by programmed cell death-ligand 1 (PD-L1) status (Tumor Proportion Score [TPS] ≥1% vs. <1%), taxane chemotherapy (paclitaxel vs. nab-paclitaxel) & geographic region (East Asia vs. non-East Asia)
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.64
	Confidence Interval	(2-Sided) 95% 0.49 to 0.85
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description	ORR was defined as the percentage of participants who had a Complete R...
Description	ORR was defined as the percentage of participants who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) as assessed by RECIST 1.1. ORR as assessed by blinded independent central review per RECIST 1.1 is presented.
Time Frame	Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

Outcome Measure Data

Analysis Population Description


Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy
Arm/Group Description:	Participants received pembrolizumab...	Participants received normal saline...
Arm/Group Description:	Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed	278	281
Measure Type: Number Number (95% Confidence Interval) Unit of Measure: Percentage of Participants
	57.9 (51.9 to 63.8)	38.4 (32.7 to 44.4)

4.Secondary Outcome


Title	Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Description	For participants who demonstrated a confirmed response (Complete Respo...
Description	For participants who demonstrated a confirmed response (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, DOR was defined as the time from first documented evidence of CR or PR until disease progression as assessed by RECIST 1.1 or death. DOR as assessed by blinded independent central review per RECIST 1.1 is presented.
Time Frame	Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

Outcome Measure Data

Analysis Population Description

The Intent-To-Treat population consisted of all randomized participants, regardless of whether or not they received study treatment, who demonstrated a confirmed response (CR or PR). Participants were included in the treatment arm to which they were randomized.


Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy
Arm/Group Description:	Participants received pembrolizumab...	Participants received normal saline...
Arm/Group Description:	Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed	161	108
Median (Full Range) Unit of Measure: Months
	7.7 (1.1 to 14.7)	4.8 (1.3 to 15.8)

5.Secondary Outcome


Title	Number of Participants Who Experienced an Adverse Event (AE)
Description	An AE was defined as any untoward medical occurrence in a participant ...
Description	An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE is presented.
Time Frame	Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

Outcome Measure Data

Analysis Population Description

The Safety population consisted of all participants who received ≥1 dose of study treatment.


Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy
Arm/Group Description:	Participants received pembrolizumab...	Participants received normal saline...
Arm/Group Description:	Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed	278	280
Measure Type: Count of Participants Unit of Measure: Participants
	273 98.2%	274 97.9%

6.Secondary Outcome


Title	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Description	The number of participants who discontinued study treatment due to an ...
Description	The number of participants who discontinued study treatment due to an AE is presented.
Time Frame	Up to approximately 19 months (Database cutoff date of 03-Apr-2018)

Outcome Measure Data

Analysis Population Description

The Safety population consisted of all participants who received ≥1 dose of study treatment.


Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy
Arm/Group Description:	Participants received pembrolizumab...	Participants received normal saline...
Arm/Group Description:	Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
Overall Number of Participants Analyzed	278	280
Measure Type: Count of Participants Unit of Measure: Participants
	65 23.4%	33 11.8%

Adverse Events

Time Frame	Up to approximately 19 months (Database cutoff date of 03-Apr-2018)
Adverse Event Reporting Description	Safety Population: All participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an adverse event (AE) unless considered related to study treatment. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as AEs.

Arm/Group Title	Pembrolizumab+Chemotherapy		Chemotherapy
Arm/Group Description	Participants received pembrolizumab...		Participants received normal saline...
Arm/Group Description	Participants received pembrolizumab 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.		Participants received normal saline by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS Investigator's choice of paclitaxel (200 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles) or nab-paclitaxel (100 mg/m^2 by IV infusion on Days 1, 8, 15 of each 21-day cycle for 4 cycles) PLUS carboplatin AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.
All-Cause Mortality
	Pembrolizumab+Chemotherapy		Chemotherapy
	Affected / at Risk (%)		Affected / at Risk (%)
Total	85/278 (30.58%)		120/281 (42.70%)
Serious Adverse Events Serious Adverse Events
	Pembrolizumab+Chemotherapy		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	113/278 (40.65%)		107/280 (38.21%)
Blood and lymphatic system disorders
Anaemia ^† 1	5/278 (1.80%)	5	8/280 (2.86%)	9
Eosinophilia ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Febrile neutropenia ^† 1	15/278 (5.40%)	15	10/280 (3.57%)	12
Leukopenia ^† 1	3/278 (1.08%)	3	0/280 (0.00%)	0
Neutropenia ^† 1	4/278 (1.44%)	5	7/280 (2.50%)	8
Thrombocytopenia ^† 1	5/278 (1.80%)	6	3/280 (1.07%)	4
Cardiac disorders
Acute coronary syndrome ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Atrial fibrillation ^† 1	0/278 (0.00%)	0	2/280 (0.71%)	3
Atrial flutter ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Cardiac arrest ^† 1	2/278 (0.72%)	2	2/280 (0.71%)	2
Cardiac failure ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Cardio-respiratory arrest ^† 1	0/278 (0.00%)	0	2/280 (0.71%)	2
Myocardial infarction ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Pericardial effusion ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Prinzmetal angina ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Tachycardia ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Endocrine disorders
Autoimmune thyroiditis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Hyperthyroidism ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Hypophysitis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Hypopituitarism ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Hypothyroidism ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Gastrointestinal disorders
Abdominal pain ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Colitis ^† 1	6/278 (2.16%)	6	1/280 (0.36%)	1
Diarrhoea ^† 1	7/278 (2.52%)	7	6/280 (2.14%)	6
Duodenal ulcer ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Duodenitis ^† 1	2/278 (0.72%)	3	0/280 (0.00%)	0
Enterocolitis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Gastric ulcer haemorrhage ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Ileus ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Intestinal perforation ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Nausea ^† 1	0/278 (0.00%)	0	2/280 (0.71%)	2
Pneumatosis intestinalis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Vomiting ^† 1	0/278 (0.00%)	0	3/280 (1.07%)	4
General disorders
Asthenia ^† 1	1/278 (0.36%)	1	5/280 (1.79%)	5
Chest pain ^† 1	1/278 (0.36%)	1	2/280 (0.71%)	2
Death ^† 1	4/278 (1.44%)	4	3/280 (1.07%)	3
Fatigue ^† 1	1/278 (0.36%)	1	3/280 (1.07%)	3
General physical health deterioration ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Malaise ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Multiple organ dysfunction syndrome ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Oedema peripheral ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Pyrexia ^† 1	6/278 (2.16%)	7	3/280 (1.07%)	3
Hepatobiliary disorders
Autoimmune hepatitis ^† 1	2/278 (0.72%)	2	0/280 (0.00%)	0
Cholangitis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Cholecystitis acute ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Cholelithiasis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Hepatic failure ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Immune system disorders
Amyloidosis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Drug hypersensitivity ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Infections and infestations
Appendiceal abscess ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Biliary tract infection ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Blister infected ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Bronchitis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Candida infection ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Clostridium difficile colitis ^† 1	1/278 (0.36%)	4	0/280 (0.00%)	0
Device related infection ^† 1	0/278 (0.00%)	0	2/280 (0.71%)	2
Empyema ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Hepatitis viral ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Kidney infection ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Lower respiratory tract infection ^† 1	1/278 (0.36%)	1	1/280 (0.36%)	1
Lung abscess ^† 1	2/278 (0.72%)	3	0/280 (0.00%)	0
Lung infection ^† 1	3/278 (1.08%)	3	2/280 (0.71%)	2
Meningitis pneumococcal ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Necrotising fasciitis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Oral candidiasis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Pneumonia ^† 1	16/278 (5.76%)	17	17/280 (6.07%)	19
Pneumonia bacterial ^† 1	2/278 (0.72%)	2	1/280 (0.36%)	1
Pneumonia klebsiella ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	3
Pneumonia legionella ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Prostatic abscess ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Pulmonary mycosis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Pulmonary sepsis ^† 1	1/278 (0.36%)	1	1/280 (0.36%)	1
Pyelonephritis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Sepsis ^† 1	5/278 (1.80%)	5	2/280 (0.71%)	2
Septic shock ^† 1	1/278 (0.36%)	1	3/280 (1.07%)	3
Upper respiratory tract infection ^† 1	2/278 (0.72%)	3	0/280 (0.00%)	0
Urinary tract infection ^† 1	2/278 (0.72%)	2	1/280 (0.36%)	1
Urosepsis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Injury, poisoning and procedural complications
Infusion related reaction ^† 1	4/278 (1.44%)	5	1/280 (0.36%)	1
Spinal compression fracture ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Investigations
Alanine aminotransferase increased ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Neutrophil count decreased ^† 1	3/278 (1.08%)	3	1/280 (0.36%)	1
Platelet count decreased ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
White blood cell count decreased ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite ^† 1	1/278 (0.36%)	1	2/280 (0.71%)	2
Dehydration ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Diabetes mellitus ^† 1	1/278 (0.36%)	1	1/280 (0.36%)	1
Hypercalcaemia ^† 1	0/278 (0.00%)	0	4/280 (1.43%)	4
Hyperkalaemia ^† 1	1/278 (0.36%)	1	2/280 (0.71%)	2
Hyponatraemia ^† 1	2/278 (0.72%)	3	2/280 (0.71%)	2
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	2/278 (0.72%)	2	0/280 (0.00%)	0
Back pain ^† 1	2/278 (0.72%)	2	1/280 (0.36%)	1
Muscle haemorrhage ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Myalgia ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Colon cancer ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Squamous cell carcinoma of skin ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Transitional cell carcinoma ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Tumour necrosis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Nervous system disorders
Carotid artery stenosis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Cerebral infarction ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Cerebral ischaemia ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Cerebrovascular accident ^† 1	2/278 (0.72%)	2	0/280 (0.00%)	0
Depressed level of consciousness ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Dizziness ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Epilepsy ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Headache ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Intercostal neuralgia ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Ischaemic stroke ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Neuropathy peripheral ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Sciatica ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Seizure ^† 1	2/278 (0.72%)	2	0/280 (0.00%)	0
Spinal cord compression ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Syncope ^† 1	1/278 (0.36%)	1	3/280 (1.07%)	3
Transient ischaemic attack ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Uraemic encephalopathy ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Psychiatric disorders
Confusional state ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Delirium ^† 1	1/278 (0.36%)	1	2/280 (0.71%)	2
Renal and urinary disorders
Acute kidney injury ^† 1	2/278 (0.72%)	3	4/280 (1.43%)	4
Glomerulonephritis membranous ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Nephritis ^† 1	1/278 (0.36%)	2	1/280 (0.36%)	1
Tubulointerstitial nephritis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Bronchitis chronic ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Chronic obstructive pulmonary disease ^† 1	2/278 (0.72%)	2	2/280 (0.71%)	2
Dyspnoea ^† 1	0/278 (0.00%)	0	3/280 (1.07%)	3
Epistaxis ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Haemoptysis ^† 1	5/278 (1.80%)	5	4/280 (1.43%)	4
Haemothorax ^† 1	1/278 (0.36%)	1	1/280 (0.36%)	1
Hypoxia ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Interstitial lung disease ^† 1	2/278 (0.72%)	2	2/280 (0.71%)	2
Obstructive airways disorder ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Pleural effusion ^† 1	3/278 (1.08%)	4	2/280 (0.71%)	3
Pneumonia aspiration ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Pneumonitis ^† 1	7/278 (2.52%)	7	2/280 (0.71%)	2
Pneumothorax ^† 1	2/278 (0.72%)	2	1/280 (0.36%)	1
Pulmonary embolism ^† 1	2/278 (0.72%)	2	3/280 (1.07%)	3
Pulmonary haemorrhage ^† 1	3/278 (1.08%)	3	2/280 (0.71%)	2
Pulmonary oedema ^† 1	1/278 (0.36%)	1	1/280 (0.36%)	1
Respiratory failure ^† 1	3/278 (1.08%)	3	0/280 (0.00%)	0
Skin and subcutaneous tissue disorders
Diabetic foot ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Psoriasis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Rash maculo-papular ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Vascular disorders
Arterial disorder ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Circulatory collapse ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Deep vein thrombosis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Embolism ^† 1	1/278 (0.36%)	1	1/280 (0.36%)	1
Hypotension ^† 1	2/278 (0.72%)	2	3/280 (1.07%)	3
Orthostatic hypotension ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Superior vena cava syndrome ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Thrombophlebitis superficial ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
Trousseau's syndrome ^† 1	0/278 (0.00%)	0	1/280 (0.36%)	1
Vasculitis ^† 1	1/278 (0.36%)	1	0/280 (0.00%)	0
1 Term from vocabulary, MedDRA 20.1 † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pembrolizumab+Chemotherapy		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	268/278 (96.40%)		267/280 (95.36%)
Blood and lymphatic system disorders
Anaemia ^† 1	144/278 (51.80%)	180	138/280 (49.29%)	170
Leukopenia ^† 1	22/278 (7.91%)	57	20/280 (7.14%)	35
Neutropenia ^† 1	101/278 (36.33%)	205	86/280 (30.71%)	160
Thrombocytopenia ^† 1	80/278 (28.78%)	127	64/280 (22.86%)	87
Endocrine disorders
Hyperthyroidism ^† 1	19/278 (6.83%)	19	2/280 (0.71%)	2
Hypothyroidism ^† 1	21/278 (7.55%)	21	5/280 (1.79%)	5
Gastrointestinal disorders
Abdominal pain ^† 1	19/278 (6.83%)	21	15/280 (5.36%)	15
Constipation ^† 1	64/278 (23.02%)	82	61/280 (21.79%)	73
Diarrhoea ^† 1	77/278 (27.70%)	111	59/280 (21.07%)	75
Nausea ^† 1	99/278 (35.61%)	140	88/280 (31.43%)	129
Vomiting ^† 1	45/278 (16.19%)	56	30/280 (10.71%)	45
General disorders
Asthenia ^† 1	59/278 (21.22%)	79	54/280 (19.29%)	63
Chest pain ^† 1	15/278 (5.40%)	15	20/280 (7.14%)	20
Fatigue ^† 1	63/278 (22.66%)	82	69/280 (24.64%)	97
Oedema peripheral ^† 1	21/278 (7.55%)	22	20/280 (7.14%)	27
Pyrexia ^† 1	30/278 (10.79%)	33	36/280 (12.86%)	42
Infections and infestations
Bronchitis ^† 1	17/278 (6.12%)	17	10/280 (3.57%)	10
Upper respiratory tract infection ^† 1	14/278 (5.04%)	16	10/280 (3.57%)	13
Investigations
Alanine aminotransferase increased ^† 1	14/278 (5.04%)	23	11/280 (3.93%)	11
Aspartate aminotransferase increased ^† 1	19/278 (6.83%)	28	12/280 (4.29%)	12
Blood creatinine increased ^† 1	21/278 (7.55%)	22	14/280 (5.00%)	19
Neutrophil count decreased ^† 1	21/278 (7.55%)	43	27/280 (9.64%)	57
Platelet count decreased ^† 1	24/278 (8.63%)	32	20/280 (7.14%)	38
Weight decreased ^† 1	28/278 (10.07%)	28	21/280 (7.50%)	21
White blood cell count decreased ^† 1	30/278 (10.79%)	58	30/280 (10.71%)	55
Metabolism and nutrition disorders
Decreased appetite ^† 1	68/278 (24.46%)	104	81/280 (28.93%)	99
Hypocalcaemia ^† 1	6/278 (2.16%)	9	15/280 (5.36%)	19
Hypokalaemia ^† 1	17/278 (6.12%)	19	17/280 (6.07%)	20
Hypomagnesaemia ^† 1	23/278 (8.27%)	30	20/280 (7.14%)	22
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	55/278 (19.78%)	78	40/280 (14.29%)	49
Back pain ^† 1	14/278 (5.04%)	14	31/280 (11.07%)	31
Musculoskeletal pain ^† 1	22/278 (7.91%)	25	13/280 (4.64%)	13
Myalgia ^† 1	37/278 (13.31%)	46	34/280 (12.14%)	40
Pain in extremity ^† 1	24/278 (8.63%)	33	25/280 (8.93%)	33
Nervous system disorders
Dizziness ^† 1	17/278 (6.12%)	20	19/280 (6.79%)	21
Dysgeusia ^† 1	25/278 (8.99%)	27	11/280 (3.93%)	11
Headache ^† 1	19/278 (6.83%)	20	21/280 (7.50%)	24
Neuropathy peripheral ^† 1	56/278 (20.14%)	61	45/280 (16.07%)	53
Paraesthesia ^† 1	18/278 (6.47%)	19	15/280 (5.36%)	16
Peripheral sensory neuropathy ^† 1	32/278 (11.51%)	33	36/280 (12.86%)	37
Psychiatric disorders
Insomnia ^† 1	28/278 (10.07%)	29	23/280 (8.21%)	26
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	37/278 (13.31%)	41	47/280 (16.79%)	54
Dyspnoea ^† 1	36/278 (12.95%)	37	42/280 (15.00%)	44
Epistaxis ^† 1	27/278 (9.71%)	31	18/280 (6.43%)	20
Haemoptysis ^† 1	21/278 (7.55%)	21	26/280 (9.29%)	37
Skin and subcutaneous tissue disorders
Alopecia ^† 1	128/278 (46.04%)	128	102/280 (36.43%)	102
Pruritus ^† 1	36/278 (12.95%)	40	21/280 (7.50%)	25
Rash ^† 1	39/278 (14.03%)	47	28/280 (10.00%)	32
Vascular disorders
Hypotension ^† 1	11/278 (3.96%)	12	15/280 (5.36%)	16
1 Term from vocabulary, MedDRA 20.1 † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.

Results Point of Contact

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Name/Title:	Senior Vice President, Global Clinical Development
Organization:	Merck Sharp & Dohme LLC
Phone:	1-800-672-6372
EMail:	ClinicalTrialsDisclosure@merck.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Paz-Ares L, Vicente D, Tafreshi A, Robinson A, Soto Parra H, Mazieres J, Hermes B, Cicin I, Medgyasszay B, Rodriguez-Cid J, Okamoto I, Lee S, Ramlau R, Vladimirov V, Cheng Y, Deng X, Zhang Y, Bas T, Piperdi B, Halmos B. A Randomized, Placebo-Controlled Trial of Pembrolizumab Plus Chemotherapy in Patients With Metastatic Squamous NSCLC: Protocol-Specified Final Analysis of KEYNOTE-407. J Thorac Oncol. 2020 Oct;15(10):1657-1669. doi: 10.1016/j.jtho.2020.06.015. Epub 2020 Jun 26.

Mazieres J, Kowalski D, Luft A, Vicente D, Tafreshi A, Gumus M, Laktionov K, Hermes B, Cicin I, Rodriguez-Cid J, Wilson J, Kato T, Ramlau R, Novello S, Reddy S, Kopp HG, Piperdi B, Li X, Burke T, Paz-Ares L. Health-Related Quality of Life With Carboplatin-Paclitaxel or nab-Paclitaxel With or Without Pembrolizumab in Patients With Metastatic Squamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Jan 20;38(3):271-280. doi: 10.1200/JCO.19.01348. Epub 2019 Nov 21.

Paz-Ares L, Luft A, Vicente D, Tafreshi A, Gumus M, Mazieres J, Hermes B, Cay Senler F, Csoszi T, Fulop A, Rodriguez-Cid J, Wilson J, Sugawara S, Kato T, Lee KH, Cheng Y, Novello S, Halmos B, Li X, Lubiniecki GM, Piperdi B, Kowalski DM; KEYNOTE-407 Investigators. Pembrolizumab plus Chemotherapy for Squamous Non-Small-Cell Lung Cancer. N Engl J Med. 2018 Nov 22;379(21):2040-2051. doi: 10.1056/NEJMoa1810865. Epub 2018 Sep 25.

Layout table for additonal information

Responsible Party:	Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:	NCT02775435
Other Study ID Numbers:	3475-407 173568 ( Registry Identifier: JAPIC-CTI ) MK-3475-407 ( Other Identifier: Merck Protocol Number ) KEYNOTE-407 ( Other Identifier: Merck ) 2016-000229-38 ( EudraCT Number )
First Submitted:	May 15, 2016
First Posted:	May 17, 2016
Results First Submitted:	February 19, 2019
Results First Posted:	April 10, 2019
Last Update Posted:	October 6, 2023

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