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)-China Extension Study

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03875092
• Collaborator: (none)
• Enrollment: 125
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 71
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

In this China extension study, carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) with or without pembrolizumab (MK-3475, KEYTRUDA®) will be administered to Chinese adults with first line metastatic squamous non-small cell lung cancer (NSCLC).

The primary hypotheses are that treatment with pembrolizumab prolongs: 1) Progression-free Survival (PFS) by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by a blinded central imaging vendor compared to placebo, and 2) Overall Survival (OS) in Chinese participants.

After analysis of interim results was conducted, the protocol was amended (Amendment 5) to allow participants the option to discontinue placebo in the control arm and to switch to pembrolizumab in the event of documented progressive disease as assessed by central review.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Biological: Pembrolizumab; Drug: Paclitaxel; Drug: Nab-paclitaxel; Drug: Carboplatin; Drug: Saline placebo for pembrolizumab	Phase 3

Detailed Description

The MK-3475-407-China Extension Study has enrolled a total of 125 participants, of which 15 participants have been also previously enrolled in the MK-3475-407 global study (NCT02775435).

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Phase III Study of Carboplatin-Paclitaxel/Nab-Paclitaxel Chemotherapy With or Without Pembrolizumab (MK-3475) in First Line Metastatic Squamous Non-small Cell Lung Cancer Subjects (KEYNOTE-407)
• Actual Study Start Date: Apr 21, 2017
• Actual Primary Completion Date: Sep 30, 2020
• Anticipated Study Completion Date: Mar 21, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab + Chemotherapy Participants receive 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 the Curve (AUC) 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles.	Biological: Pembrolizumab; IV infusion; Other Names: MK-3475 KEYTRUDA® ; Drug: Paclitaxel; IV infusion; Other Names: TAXOL® ; Drug: Nab-paclitaxel; IV infusion; Other Names: ABRAXANE® ; Drug: Carboplatin; IV infusion Carboplatin dose should not exceed 900 mg.; Other Names: PARAPLATIN®
Active Comparator: Chemotherapy Participants receive 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.	Drug: Paclitaxel; IV infusion; Other Names: TAXOL® ; Drug: Nab-paclitaxel; IV infusion; Other Names: ABRAXANE® ; Drug: Carboplatin; IV infusion Carboplatin dose should not exceed 900 mg.; Other Names: PARAPLATIN® ; Drug: Saline placebo for pembrolizumab; IV infusion

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 33 months (Database cutoff date of 30-Sep-2020)]

   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. Data are from the product-limit (Kaplan-Meier) method for censored data.

2. Overall Survival (OS) [Up to approximately 39 months (Database cutoff date of 30-Sep-2020)]

   OS was defined as the time from randomization to death due to any cause. OS is presented. Data are from the product-limit (Kaplan-Meier) method for censored data.

Secondary Outcome Measures

1. Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 33 months (Database cutoff date of 30-Sep-2020)]

   ORR was defined as the percentage of participants in the analysis population 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.

2. Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 30 months (Database cutoff date of 30-Sep-2020)]

   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.

3. Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 31 months (Database cutoff date of 30-Sep-2020)]

   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. Data are from the product-limit (Kaplan-Meier) method for censored data.

4. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [Up to approximately 29 months (Database cutoff date of 30-Sep-2020)]

   The number of participants who discontinued study treatment due to an AE is presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b-American Joint Committee on Cancer [AJCC]) squamous NSCLC.

• Has measurable disease based on RECIST 1.1 as determined by the local site investigator/radiology assessment.

• Has not received prior systemic treatment for metastatic NSCLC.

• Has provided tumor tissue from locations not radiated prior to biopsy.

• Has a life expectancy of at least 3 months.

• Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status.

• Has adequate organ function.

• If female of childbearing potential, is willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of study treatment.

• If male with a female partner(s) of child-bearing potential, must agree to use an adequate method of contraception starting with the first dose of study treatment through 95 days after the last dose of study treatment. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner.

Exclusion Criteria:

• Has non-squamous histology NSCLC.

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to administration of pembrolizumab.

• Before the first dose of study drug: a) Has received prior systemic cytotoxic chemotherapy for metastatic disease; b) Has received other targeted or biological antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease; c) Has had major surgery (<3 weeks prior to first dose).

• Received radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment.

• Completed palliative radiotherapy within 7 days of the first dose of study treatment.

• Is expected to require any other form of antineoplastic therapy while on study.

• Has received a live-virus vaccination within 30 days of planned treatment start.

• Has a known history of prior malignancy except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy.

• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.

• Has pre-existing peripheral neuropathy that is ≥ Grade 2 by Common Terminology Criteria for Adverse Events (CTCAE) Version 4 criteria.

• Previously had a severe hypersensitivity reaction to treatment with another monoclonal antibody.

• Has a known sensitivity to any component of carboplatin or paclitaxel or nab-paclitaxel.

• Has active autoimmune disease that has required systemic treatment in past 2 years.

• Is on chronic systemic steroids.

• Had prior treatment with any other anti-programmed cell death 1 (anti-PD-1), or programmed cell death ligand 1 (PD-L1) or PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors or mechanisms.

• Has participated in any other pembrolizumab trial and has been treated with pembrolizumab.

• Has an active infection requiring therapy.

• Has known history of Human Immunodeficiency Virus (HIV).

• Has known active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection.

• Is, at the time of providing documented informed consent, a regular user (including "recreational use") of any illicit drugs or has a recent history (within the last year) of substance abuse (including alcohol).

• Has interstitial lung disease or a history of pneumonitis that required oral or intravenous glucocorticoids to assist with management.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Zhongshan Hospital Fudan University	Shanghai		China	200032

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol - Oct 30, 2019
• Statistical Analysis Plan - Jan 29, 2018

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03875092
• Other Study ID Numbers: 3475-407 China Extension; 173568; MK-3475-407; KEYNOTE-407
• First Posted: Mar 14, 2019
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck Sharp & Dohme LLC: Programmed Cell Death-1 (PD1, PD-1); Programmed Death-Ligand 1 (PDL1, PD-L1)
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Albumin-Bound Paclitaxel; Carboplatin; Pembrolizumab

Study Results

Participant Flow

Recruitment Details	Interim analysis data cutoff date: 30-Sep-2020. Of the 125 randomized participants in the China Extension Study, 49 were ongoing and 38 participants who randomized to chemotherapy had switched to receiving protocol-specified pembrolizumab (MK-3475). Interim results are for randomized treatment only.

Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy
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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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	65	60
Treated	65	60
Switched to Pembrolizumab+Chemotherapy	0	38
COMPLETED	0	0
NOT COMPLETED	65	60

Baseline Characteristics

Arm/Group Title	Pembrolizumab + Chemotherapy	Chemotherapy	Total
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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 Participants	65	60	125
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.6 (8.7)	61.5 (9.1)	61.5 (8.8)
Sex: Female, Male (Count of Participants)
Female	3 4.6%	3 5%	6 4.8%
Male	62 95.4%	57 95%	119 95.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	65 100%	60 100%	125 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	65 100%	60 100%	125 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Level: Tumor Proportion Score (TPS) (Count of Participants)
TPS <1%	25 38.5%	23 38.3%	48 38.4%
TPS ≥1%	37 56.9%	35 58.3%	72 57.6%
Unknown	3 4.6%	2 3.3%	5 4%
Taxane Chemotherapy (Count of Participants)
+Paclitaxel	65 100%	60 100%	125 100%
+Nab-paclitaxel	0 0%	0 0%	0 0%
Geographic Region (Count of Participants)
East Asia	65 100%	60 100%	125 100%
Non-East Asia	0 0%	0 0%	0 0%

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 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. Data are from the product-limit (Kaplan-Meier) method for censored data.
Time Frame	Up to approximately 33 months (Database cutoff date of 30-Sep-2020)

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 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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.
Measure Participants	65	60
Median (95% Confidence Interval) [Months]	8.3	4.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab + Chemotherapy, Chemotherapy
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95%; 0.24 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on unstratified Cox regression model with treatment as a covariate, due to small sample size.

2. Primary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death due to any cause. OS is presented. Data are from the product-limit (Kaplan-Meier) method for censored data.
Time Frame	Up to approximately 39 months (Database cutoff date of 30-Sep-2020)

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 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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.
Measure Participants	65	60
Median (95% Confidence Interval) [Months]	30.1	12.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab + Chemotherapy, Chemotherapy
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.44
	Confidence Interval	(2-Sided) 95%; 0.28 to 0.70
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on unstratified Cox regression model with treatment as a covariate, due to small sample size.

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 in the analysis population 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 33 months (Database cutoff date of 30-Sep-2020)

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 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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.
Measure Participants	65	60
Number (95% Confidence Interval) [Percentage of Participants]	80.0 123.1%	43.3 72.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab + Chemotherapy, Chemotherapy
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	36.7
	Confidence Interval	(2-Sided) 95%; 19.9 to 51.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

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 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 30 months (Database cutoff date of 30-Sep-2020)

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 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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.
Measure Participants	65	60
Median (95% Confidence Interval) [Months]	7.1	3.5

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 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. Data are from the product-limit (Kaplan-Meier) method for censored data.
Time Frame	Up to approximately 31 months (Database cutoff date of 30-Sep-2020)

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 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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.
Measure Participants	65	60
Count of Participants [Participants]	65 100%	60 100%

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 AE is presented.
Time Frame	Up to approximately 29 months (Database cutoff date of 30-Sep-2020)

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 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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.
Measure Participants	65	60
Count of Participants [Participants]	8 12.3%	4 6.7%

Adverse Events

Time Frame	Up to approximately 39 months (Database cutoff date of 30-Sep-2020) for All-Cause Mortality. Up to approximately 31 months for adverse events. All use a database cutoff date of 30-Sep-2020.
Adverse Event Reporting Description	Mortality data were collected for all randomized participants. Adverse event (AE) data were collected for all participants who received ≥1 dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Therefore Medical Dictionary for Regulatory Activities (MedDRA) 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 200 mg by IV infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles PLUS paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 paclitaxel (200 mg/m^2 by IV infusion on Day 1 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 (%)	# Events	Affected / at Risk (%)	# Events
Total	30/65 (46.2%)		46/60 (76.7%)
Serious Adverse Events
	Pembrolizumab + Chemotherapy		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/65 (52.3%)		22/60 (36.7%)
Blood and lymphatic system disorders
Febrile neutropenia	3/65 (4.6%)	4	3/60 (5%)	3
Leukopenia	3/65 (4.6%)	4	0/60 (0%)	0
Neutropenia	5/65 (7.7%)	6	1/60 (1.7%)	1
Thrombocytopenia	4/65 (6.2%)	5	2/60 (3.3%)	2
Cardiac disorders
Angina unstable	1/65 (1.5%)	1	0/60 (0%)	0
Coronary artery disease	1/65 (1.5%)	1	0/60 (0%)	0
Myocardial infarction	1/65 (1.5%)	1	0/60 (0%)	0
Endocrine disorders
Hypothyroidism	1/65 (1.5%)	1	0/60 (0%)	0
Gastrointestinal disorders
Colitis	1/65 (1.5%)	1	0/60 (0%)	0
Diarrhoea	1/65 (1.5%)	1	0/60 (0%)	0
Gastritis	0/65 (0%)	0	1/60 (1.7%)	1
Gastrointestinal perforation	0/65 (0%)	0	1/60 (1.7%)	1
Intestinal obstruction	0/65 (0%)	0	1/60 (1.7%)	1
Lower gastrointestinal haemorrhage	1/65 (1.5%)	1	0/60 (0%)	0
General disorders
Chest pain	0/65 (0%)	0	1/60 (1.7%)	1
Malaise	1/65 (1.5%)	1	0/60 (0%)	0
Pyrexia	0/65 (0%)	0	2/60 (3.3%)	2
Hepatobiliary disorders
Bile duct stone	1/65 (1.5%)	1	0/60 (0%)	0
Hepatic function abnormal	0/65 (0%)	0	1/60 (1.7%)	1
Immune system disorders
Anaphylactic shock	1/65 (1.5%)	1	0/60 (0%)	0
Infections and infestations
Appendicitis	1/65 (1.5%)	1	0/60 (0%)	0
Pneumonia	5/65 (7.7%)	7	5/60 (8.3%)	5
Pulmonary mycosis	0/65 (0%)	0	1/60 (1.7%)	1
Pulmonary tuberculosis	1/65 (1.5%)	1	0/60 (0%)	0
Upper respiratory tract infection	2/65 (3.1%)	3	0/60 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	1/65 (1.5%)	1	0/60 (0%)	0
Investigations
Alanine aminotransferase increased	1/65 (1.5%)	1	0/60 (0%)	0
Neutrophil count decreased	2/65 (3.1%)	2	0/60 (0%)	0
Platelet count decreased	1/65 (1.5%)	1	1/60 (1.7%)	1
Metabolism and nutrition disorders
Decreased appetite	1/65 (1.5%)	1	1/60 (1.7%)	1
Diabetic ketoacidosis	2/65 (3.1%)	2	0/60 (0%)	0
Hyponatraemia	1/65 (1.5%)	2	0/60 (0%)	0
Type 1 diabetes mellitus	1/65 (1.5%)	1	0/60 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/65 (0%)	0	1/60 (1.7%)	1
Nervous system disorders
Cerebral haemorrhage	1/65 (1.5%)	1	0/60 (0%)	0
Cerebral infarction	1/65 (1.5%)	1	1/60 (1.7%)	1
Renal and urinary disorders
Acute kidney injury	1/65 (1.5%)	1	0/60 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/65 (0%)	0	1/60 (1.7%)	1
Haemoptysis	0/65 (0%)	0	2/60 (3.3%)	2
Interstitial lung disease	1/65 (1.5%)	1	0/60 (0%)	0
Pneumonitis	1/65 (1.5%)	1	1/60 (1.7%)	1
Pneumothorax	1/65 (1.5%)	1	0/60 (0%)	0
Pulmonary embolism	1/65 (1.5%)	1	0/60 (0%)	0
Vascular disorders
Deep vein thrombosis	1/65 (1.5%)	1	1/60 (1.7%)	1
Peripheral arterial occlusive disease	1/65 (1.5%)	1	0/60 (0%)	0
Peripheral artery aneurysm	1/65 (1.5%)	1	0/60 (0%)	0
Peripheral artery thrombosis	1/65 (1.5%)	2	0/60 (0%)	0
Superior vena cava syndrome	0/65 (0%)	0	1/60 (1.7%)	1
Other (Not Including Serious) Adverse Events
	Pembrolizumab + Chemotherapy		Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	65/65 (100%)		60/60 (100%)
Blood and lymphatic system disorders
Anaemia	42/65 (64.6%)	103	46/60 (76.7%)	85
Leukopenia	12/65 (18.5%)	49	7/60 (11.7%)	32
Thrombocytopenia	4/65 (6.2%)	6	3/60 (5%)	4
Cardiac disorders
Atrial fibrillation	0/65 (0%)	0	4/60 (6.7%)	4
Endocrine disorders
Hyperthyroidism	11/65 (16.9%)	15	1/60 (1.7%)	1
Hypothyroidism	8/65 (12.3%)	15	1/60 (1.7%)	1
Gastrointestinal disorders
Abdominal pain	4/65 (6.2%)	4	1/60 (1.7%)	1
Constipation	16/65 (24.6%)	20	14/60 (23.3%)	21
Diarrhoea	11/65 (16.9%)	23	6/60 (10%)	11
Nausea	24/65 (36.9%)	42	13/60 (21.7%)	22
Vomiting	15/65 (23.1%)	26	10/60 (16.7%)	12
General disorders
Asthenia	10/65 (15.4%)	16	7/60 (11.7%)	9
Chest discomfort	5/65 (7.7%)	5	1/60 (1.7%)	1
Chest pain	4/65 (6.2%)	4	9/60 (15%)	10
Fatigue	5/65 (7.7%)	13	3/60 (5%)	8
Malaise	8/65 (12.3%)	9	8/60 (13.3%)	9
Pyrexia	12/65 (18.5%)	14	9/60 (15%)	10
Hepatobiliary disorders
Hyperbilirubinaemia	4/65 (6.2%)	6	3/60 (5%)	4
Infections and infestations
Pneumonia	7/65 (10.8%)	8	6/60 (10%)	7
Upper respiratory tract infection	9/65 (13.8%)	12	3/60 (5%)	5
Investigations
Alanine aminotransferase increased	23/65 (35.4%)	39	17/60 (28.3%)	26
Aspartate aminotransferase increased	18/65 (27.7%)	31	13/60 (21.7%)	21
Bilirubin conjugated increased	3/65 (4.6%)	18	4/60 (6.7%)	5
Blood albumin decreased	4/65 (6.2%)	9	2/60 (3.3%)	3
Blood alkaline phosphatase increased	7/65 (10.8%)	15	3/60 (5%)	4
Blood bilirubin increased	5/65 (7.7%)	26	4/60 (6.7%)	5
Blood creatinine increased	4/65 (6.2%)	11	4/60 (6.7%)	4
Blood uric acid increased	5/65 (7.7%)	14	3/60 (5%)	3
Gamma-glutamyltransferase increased	10/65 (15.4%)	12	11/60 (18.3%)	14
Neutrophil count decreased	50/65 (76.9%)	195	43/60 (71.7%)	128
Neutrophil count increased	1/65 (1.5%)	1	5/60 (8.3%)	6
Platelet count decreased	16/65 (24.6%)	53	22/60 (36.7%)	37
Weight decreased	9/65 (13.8%)	9	11/60 (18.3%)	13
Weight increased	8/65 (12.3%)	11	2/60 (3.3%)	2
White blood cell count decreased	51/65 (78.5%)	192	42/60 (70%)	131
White blood cell count increased	1/65 (1.5%)	1	4/60 (6.7%)	5
Metabolism and nutrition disorders
Decreased appetite	25/65 (38.5%)	43	19/60 (31.7%)	25
Hyperglycaemia	13/65 (20%)	20	7/60 (11.7%)	13
Hyperuricaemia	10/65 (15.4%)	31	3/60 (5%)	5
Hypoalbuminaemia	9/65 (13.8%)	12	13/60 (21.7%)	18
Hypocalcaemia	5/65 (7.7%)	9	1/60 (1.7%)	1
Hypochloraemia	6/65 (9.2%)	8	4/60 (6.7%)	5
Hypokalaemia	16/65 (24.6%)	34	12/60 (20%)	20
Hyponatraemia	10/65 (15.4%)	18	10/60 (16.7%)	14
Hypoproteinaemia	2/65 (3.1%)	2	4/60 (6.7%)	5
Musculoskeletal and connective tissue disorders
Arthralgia	23/65 (35.4%)	43	14/60 (23.3%)	19
Bone pain	3/65 (4.6%)	3	5/60 (8.3%)	8
Myalgia	13/65 (20%)	19	8/60 (13.3%)	10
Pain in extremity	14/65 (21.5%)	17	13/60 (21.7%)	13
Nervous system disorders
Hypoaesthesia	29/65 (44.6%)	46	22/60 (36.7%)	25
Neuropathy peripheral	6/65 (9.2%)	6	8/60 (13.3%)	8
Paraesthesia	6/65 (9.2%)	7	2/60 (3.3%)	2
Psychiatric disorders
Insomnia	10/65 (15.4%)	14	2/60 (3.3%)	3
Respiratory, thoracic and mediastinal disorders
Cough	9/65 (13.8%)	9	4/60 (6.7%)	4
Dyspnoea	5/65 (7.7%)	6	7/60 (11.7%)	10
Haemoptysis	5/65 (7.7%)	5	12/60 (20%)	16
Hiccups	11/65 (16.9%)	18	3/60 (5%)	6
Productive cough	5/65 (7.7%)	5	2/60 (3.3%)	2
Skin and subcutaneous tissue disorders
Alopecia	51/65 (78.5%)	53	40/60 (66.7%)	40
Pruritus	6/65 (9.2%)	6	3/60 (5%)	3
Rash	16/65 (24.6%)	23	3/60 (5%)	4
Rash maculo-papular	4/65 (6.2%)	4	2/60 (3.3%)	3
Vascular disorders
Hypertension	4/65 (6.2%)	4	2/60 (3.3%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.