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)
Sponsor
Merck Sharp & Dohme LLC (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT02775435
Collaborator
(none)
559
2
81.3
Study Details
Study Description
Brief Summary
This is a study of carboplatin and paclitaxel or nano particle albumin-bound paclitaxel (nab-paclitaxel) with or without pembrolizumab (MK-3475, KEYTRUDA®) in 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).
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 |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
559 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
:
Jun 9, 2016
Actual Primary Completion Date
:
Apr 3, 2018
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 AUC 6 by IV infusion on Day 1 of each 21-day cycle for 4 cycles. |
Biological: Pembrolizumab
IV infusion
Other Names:
Drug: Paclitaxel
IV infusion
Other Names:
Drug: Nab-paclitaxel
IV infusion
Other Names:
Drug: Carboplatin
IV infusion Carboplatin dose should not to exceed 900 mg.
Other Names:
|
| 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:
Drug: Nab-paclitaxel
IV infusion
Other Names:
Drug: Carboplatin
IV infusion Carboplatin dose should not to exceed 900 mg.
Other Names:
Drug: Saline placebo for pembrolizumab
IV infusion
|
Outcome Measures
Primary Outcome Measures
- Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 19 months (Database cutoff date of 03-Apr-2018)]
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.
- Overall Survival (OS) [Up to approximately 19 months (Database cutoff date of 03-Apr-2018)]
OS was defined as the time from randomization to death due to any cause. OS is presented.
Secondary Outcome Measures
- Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 19 months (Database cutoff date of 03-Apr-2018)]
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.
- Duration of Response (DOR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [Up to approximately 19 months (Database cutoff date of 03-Apr-2018)]
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.
- Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 19 months (Database cutoff date of 03-Apr-2018)]
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.
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [Up to approximately 19 months (Database cutoff date of 03-Apr-2018)]
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] 7th edition) 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 drug.
-
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 drug through 95 days after the last dose of study drug. 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 Gy within 6 months of the first dose of study drug.
-
Completed palliative radiotherapy within 7 days of the first dose of study drug.
-
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 or C. Active Hepatitis B.
-
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
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT02775435
Other Study ID Numbers:
- 3475-407
- 173568
- MK-3475-407
- KEYNOTE-407
- 2016-000229-38
First Posted:
May 17, 2016
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
Additional relevant MeSH terms:
Study Results
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 Detail |
| Arm/Group Title | Pembrolizumab + Chemotherapy | Chemotherapy |
|---|---|---|
| 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 |
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 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 Participants | 278 | 281 | 559 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
65.0
(8.8)
|
64.8
(8.7)
|
64.9
(8.7)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
58
20.9%
|
46
16.4%
|
104
18.6%
|
| Male |
220
79.1%
|
235
83.6%
|
455
81.4%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
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%
|
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%
|
| Unknown or Not Reported |
2
0.7%
|
9
3.2%
|
11
2%
|
| Programmed Cell Death-Ligand 1 (PD-L1) Tumor Expression Level: Tumor Proportion Score (TPS) (Count of Participants) | |||
| TPS <1% |
95
34.2%
|
99
35.2%
|
194
34.7%
|
| TPS ≥1% |
176
63.3%
|
177
63%
|
353
63.1%
|
| Unknown |
7
2.5%
|
5
1.8%
|
12
2.1%
|
| Taxane Chemotherapy (Count of Participants) | |||
| +Paclitaxel |
169
60.8%
|
167
59.4%
|
336
60.1%
|
| +Nab-paclitaxel |
109
39.2%
|
114
40.6%
|
223
39.9%
|
| Geographic Region (Count of Participants) | |||
| East Asia |
54
19.4%
|
52
18.5%
|
106
19%
|
| Non-East Asia |
224
80.6%
|
229
81.5%
|
453
81%
|
Outcome Measures
| 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. |
| 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 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. |
| Measure Participants | 278 | 281 |
| Median (95% Confidence Interval) [Months] |
6.4
|
4.8
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab + Chemotherapy, Chemotherapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| 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 | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.56 | |
| Confidence Interval |
(2-Sided) 95% 0.45 to 0.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival (OS) |
|---|---|
| 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 |
|---|
| 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 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. |
| Measure Participants | 278 | 281 |
| Median (95% Confidence Interval) [Months] |
15.9
|
11.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab + Chemotherapy, Chemotherapy |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| 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 | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.64 | |
| Confidence Interval |
(2-Sided) 95% 0.49 to 0.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 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 |
|---|
| 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 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. |
| Measure Participants | 278 | 281 |
| Number (95% Confidence Interval) [Percentage of Participants] |
57.9
20.8%
|
38.4
13.7%
|
| 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 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 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. |
| Measure Participants | 161 | 108 |
| Median (Full Range) [Months] |
7.7
|
4.8
|
| 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. |
| 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 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. |
| Measure Participants | 278 | 280 |
| Count of Participants [Participants] |
273
98.2%
|
274
97.5%
|
| 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 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 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. |
| Measure Participants | 278 | 280 |
| Count of Participants [Participants] |
65
23.4%
|
33
11.7%
|
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 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 85/278 (30.6%) | 120/281 (42.7%) | ||
Serious Adverse Events |
||||
| Pembrolizumab+Chemotherapy | Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 113/278 (40.6%) | 107/280 (38.2%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 5/278 (1.8%) | 5 | 8/280 (2.9%) | 9 |
| Eosinophilia | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Febrile neutropenia | 15/278 (5.4%) | 15 | 10/280 (3.6%) | 12 |
| Leukopenia | 3/278 (1.1%) | 3 | 0/280 (0%) | 0 |
| Neutropenia | 4/278 (1.4%) | 5 | 7/280 (2.5%) | 8 |
| Thrombocytopenia | 5/278 (1.8%) | 6 | 3/280 (1.1%) | 4 |
| Cardiac disorders | ||||
| Acute coronary syndrome | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Atrial fibrillation | 0/278 (0%) | 0 | 2/280 (0.7%) | 3 |
| Atrial flutter | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Cardiac arrest | 2/278 (0.7%) | 2 | 2/280 (0.7%) | 2 |
| Cardiac failure | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Cardio-respiratory arrest | 0/278 (0%) | 0 | 2/280 (0.7%) | 2 |
| Myocardial infarction | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Pericardial effusion | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Prinzmetal angina | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Tachycardia | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Endocrine disorders | ||||
| Autoimmune thyroiditis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Hyperthyroidism | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Hypophysitis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Hypopituitarism | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Hypothyroidism | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Colitis | 6/278 (2.2%) | 6 | 1/280 (0.4%) | 1 |
| Diarrhoea | 7/278 (2.5%) | 7 | 6/280 (2.1%) | 6 |
| Duodenal ulcer | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Duodenitis | 2/278 (0.7%) | 3 | 0/280 (0%) | 0 |
| Enterocolitis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Gastric ulcer haemorrhage | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Ileus | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Intestinal perforation | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Nausea | 0/278 (0%) | 0 | 2/280 (0.7%) | 2 |
| Pneumatosis intestinalis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Vomiting | 0/278 (0%) | 0 | 3/280 (1.1%) | 4 |
| General disorders | ||||
| Asthenia | 1/278 (0.4%) | 1 | 5/280 (1.8%) | 5 |
| Chest pain | 1/278 (0.4%) | 1 | 2/280 (0.7%) | 2 |
| Death | 4/278 (1.4%) | 4 | 3/280 (1.1%) | 3 |
| Fatigue | 1/278 (0.4%) | 1 | 3/280 (1.1%) | 3 |
| General physical health deterioration | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Malaise | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Multiple organ dysfunction syndrome | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Oedema peripheral | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Pyrexia | 6/278 (2.2%) | 7 | 3/280 (1.1%) | 3 |
| Hepatobiliary disorders | ||||
| Autoimmune hepatitis | 2/278 (0.7%) | 2 | 0/280 (0%) | 0 |
| Cholangitis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Cholecystitis acute | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Cholelithiasis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Hepatic failure | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Immune system disorders | ||||
| Amyloidosis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Drug hypersensitivity | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Infections and infestations | ||||
| Appendiceal abscess | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Biliary tract infection | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Blister infected | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Bronchitis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Candida infection | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Clostridium difficile colitis | 1/278 (0.4%) | 4 | 0/280 (0%) | 0 |
| Device related infection | 0/278 (0%) | 0 | 2/280 (0.7%) | 2 |
| Empyema | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Hepatitis viral | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Kidney infection | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Lower respiratory tract infection | 1/278 (0.4%) | 1 | 1/280 (0.4%) | 1 |
| Lung abscess | 2/278 (0.7%) | 3 | 0/280 (0%) | 0 |
| Lung infection | 3/278 (1.1%) | 3 | 2/280 (0.7%) | 2 |
| Meningitis pneumococcal | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Necrotising fasciitis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Oral candidiasis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Pneumonia | 16/278 (5.8%) | 17 | 17/280 (6.1%) | 19 |
| Pneumonia bacterial | 2/278 (0.7%) | 2 | 1/280 (0.4%) | 1 |
| Pneumonia klebsiella | 0/278 (0%) | 0 | 1/280 (0.4%) | 3 |
| Pneumonia legionella | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Prostatic abscess | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Pulmonary mycosis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Pulmonary sepsis | 1/278 (0.4%) | 1 | 1/280 (0.4%) | 1 |
| Pyelonephritis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Sepsis | 5/278 (1.8%) | 5 | 2/280 (0.7%) | 2 |
| Septic shock | 1/278 (0.4%) | 1 | 3/280 (1.1%) | 3 |
| Upper respiratory tract infection | 2/278 (0.7%) | 3 | 0/280 (0%) | 0 |
| Urinary tract infection | 2/278 (0.7%) | 2 | 1/280 (0.4%) | 1 |
| Urosepsis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Infusion related reaction | 4/278 (1.4%) | 5 | 1/280 (0.4%) | 1 |
| Spinal compression fracture | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Investigations | ||||
| Alanine aminotransferase increased | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Neutrophil count decreased | 3/278 (1.1%) | 3 | 1/280 (0.4%) | 1 |
| Platelet count decreased | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| White blood cell count decreased | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 1/278 (0.4%) | 1 | 2/280 (0.7%) | 2 |
| Dehydration | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Diabetes mellitus | 1/278 (0.4%) | 1 | 1/280 (0.4%) | 1 |
| Hypercalcaemia | 0/278 (0%) | 0 | 4/280 (1.4%) | 4 |
| Hyperkalaemia | 1/278 (0.4%) | 1 | 2/280 (0.7%) | 2 |
| Hyponatraemia | 2/278 (0.7%) | 3 | 2/280 (0.7%) | 2 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 2/278 (0.7%) | 2 | 0/280 (0%) | 0 |
| Back pain | 2/278 (0.7%) | 2 | 1/280 (0.4%) | 1 |
| Muscle haemorrhage | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Myalgia | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Cancer pain | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Colon cancer | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Squamous cell carcinoma of skin | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Transitional cell carcinoma | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Tumour necrosis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Nervous system disorders | ||||
| Carotid artery stenosis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Cerebral infarction | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Cerebral ischaemia | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Cerebrovascular accident | 2/278 (0.7%) | 2 | 0/280 (0%) | 0 |
| Depressed level of consciousness | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Dizziness | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Epilepsy | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Headache | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Intercostal neuralgia | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Ischaemic stroke | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Neuropathy peripheral | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Sciatica | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Seizure | 2/278 (0.7%) | 2 | 0/280 (0%) | 0 |
| Spinal cord compression | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Syncope | 1/278 (0.4%) | 1 | 3/280 (1.1%) | 3 |
| Transient ischaemic attack | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Uraemic encephalopathy | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Psychiatric disorders | ||||
| Confusional state | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Delirium | 1/278 (0.4%) | 1 | 2/280 (0.7%) | 2 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 2/278 (0.7%) | 3 | 4/280 (1.4%) | 4 |
| Glomerulonephritis membranous | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Nephritis | 1/278 (0.4%) | 2 | 1/280 (0.4%) | 1 |
| Tubulointerstitial nephritis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Atelectasis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Bronchitis chronic | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Chronic obstructive pulmonary disease | 2/278 (0.7%) | 2 | 2/280 (0.7%) | 2 |
| Dyspnoea | 0/278 (0%) | 0 | 3/280 (1.1%) | 3 |
| Epistaxis | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Haemoptysis | 5/278 (1.8%) | 5 | 4/280 (1.4%) | 4 |
| Haemothorax | 1/278 (0.4%) | 1 | 1/280 (0.4%) | 1 |
| Hypoxia | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Interstitial lung disease | 2/278 (0.7%) | 2 | 2/280 (0.7%) | 2 |
| Obstructive airways disorder | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Pleural effusion | 3/278 (1.1%) | 4 | 2/280 (0.7%) | 3 |
| Pneumonia aspiration | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Pneumonitis | 7/278 (2.5%) | 7 | 2/280 (0.7%) | 2 |
| Pneumothorax | 2/278 (0.7%) | 2 | 1/280 (0.4%) | 1 |
| Pulmonary embolism | 2/278 (0.7%) | 2 | 3/280 (1.1%) | 3 |
| Pulmonary haemorrhage | 3/278 (1.1%) | 3 | 2/280 (0.7%) | 2 |
| Pulmonary oedema | 1/278 (0.4%) | 1 | 1/280 (0.4%) | 1 |
| Respiratory failure | 3/278 (1.1%) | 3 | 0/280 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Diabetic foot | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Psoriasis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Rash maculo-papular | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Vascular disorders | ||||
| Arterial disorder | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Circulatory collapse | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Deep vein thrombosis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Embolism | 1/278 (0.4%) | 1 | 1/280 (0.4%) | 1 |
| Hypotension | 2/278 (0.7%) | 2 | 3/280 (1.1%) | 3 |
| Orthostatic hypotension | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Superior vena cava syndrome | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Thrombophlebitis superficial | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
| Trousseau's syndrome | 0/278 (0%) | 0 | 1/280 (0.4%) | 1 |
| Vasculitis | 1/278 (0.4%) | 1 | 0/280 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| Pembrolizumab+Chemotherapy | Chemotherapy | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 268/278 (96.4%) | 267/280 (95.4%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 144/278 (51.8%) | 180 | 138/280 (49.3%) | 170 |
| Leukopenia | 22/278 (7.9%) | 57 | 20/280 (7.1%) | 35 |
| Neutropenia | 101/278 (36.3%) | 205 | 86/280 (30.7%) | 160 |
| Thrombocytopenia | 80/278 (28.8%) | 127 | 64/280 (22.9%) | 87 |
| Endocrine disorders | ||||
| Hyperthyroidism | 19/278 (6.8%) | 19 | 2/280 (0.7%) | 2 |
| Hypothyroidism | 21/278 (7.6%) | 21 | 5/280 (1.8%) | 5 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 19/278 (6.8%) | 21 | 15/280 (5.4%) | 15 |
| Constipation | 64/278 (23%) | 82 | 61/280 (21.8%) | 73 |
| Diarrhoea | 77/278 (27.7%) | 111 | 59/280 (21.1%) | 75 |
| Nausea | 99/278 (35.6%) | 140 | 88/280 (31.4%) | 129 |
| Vomiting | 45/278 (16.2%) | 56 | 30/280 (10.7%) | 45 |
| General disorders | ||||
| Asthenia | 59/278 (21.2%) | 79 | 54/280 (19.3%) | 63 |
| Chest pain | 15/278 (5.4%) | 15 | 20/280 (7.1%) | 20 |
| Fatigue | 63/278 (22.7%) | 82 | 69/280 (24.6%) | 97 |
| Oedema peripheral | 21/278 (7.6%) | 22 | 20/280 (7.1%) | 27 |
| Pyrexia | 30/278 (10.8%) | 33 | 36/280 (12.9%) | 42 |
| Infections and infestations | ||||
| Bronchitis | 17/278 (6.1%) | 17 | 10/280 (3.6%) | 10 |
| Upper respiratory tract infection | 14/278 (5%) | 16 | 10/280 (3.6%) | 13 |
| Investigations | ||||
| Alanine aminotransferase increased | 14/278 (5%) | 23 | 11/280 (3.9%) | 11 |
| Aspartate aminotransferase increased | 19/278 (6.8%) | 28 | 12/280 (4.3%) | 12 |
| Blood creatinine increased | 21/278 (7.6%) | 22 | 14/280 (5%) | 19 |
| Neutrophil count decreased | 21/278 (7.6%) | 43 | 27/280 (9.6%) | 57 |
| Platelet count decreased | 24/278 (8.6%) | 32 | 20/280 (7.1%) | 38 |
| Weight decreased | 28/278 (10.1%) | 28 | 21/280 (7.5%) | 21 |
| White blood cell count decreased | 30/278 (10.8%) | 58 | 30/280 (10.7%) | 55 |
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 68/278 (24.5%) | 104 | 81/280 (28.9%) | 99 |
| Hypocalcaemia | 6/278 (2.2%) | 9 | 15/280 (5.4%) | 19 |
| Hypokalaemia | 17/278 (6.1%) | 19 | 17/280 (6.1%) | 20 |
| Hypomagnesaemia | 23/278 (8.3%) | 30 | 20/280 (7.1%) | 22 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 55/278 (19.8%) | 78 | 40/280 (14.3%) | 49 |
| Back pain | 14/278 (5%) | 14 | 31/280 (11.1%) | 31 |
| Musculoskeletal pain | 22/278 (7.9%) | 25 | 13/280 (4.6%) | 13 |
| Myalgia | 37/278 (13.3%) | 46 | 34/280 (12.1%) | 40 |
| Pain in extremity | 24/278 (8.6%) | 33 | 25/280 (8.9%) | 33 |
| Nervous system disorders | ||||
| Dizziness | 17/278 (6.1%) | 20 | 19/280 (6.8%) | 21 |
| Dysgeusia | 25/278 (9%) | 27 | 11/280 (3.9%) | 11 |
| Headache | 19/278 (6.8%) | 20 | 21/280 (7.5%) | 24 |
| Neuropathy peripheral | 56/278 (20.1%) | 61 | 45/280 (16.1%) | 53 |
| Paraesthesia | 18/278 (6.5%) | 19 | 15/280 (5.4%) | 16 |
| Peripheral sensory neuropathy | 32/278 (11.5%) | 33 | 36/280 (12.9%) | 37 |
| Psychiatric disorders | ||||
| Insomnia | 28/278 (10.1%) | 29 | 23/280 (8.2%) | 26 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 37/278 (13.3%) | 41 | 47/280 (16.8%) | 54 |
| Dyspnoea | 36/278 (12.9%) | 37 | 42/280 (15%) | 44 |
| Epistaxis | 27/278 (9.7%) | 31 | 18/280 (6.4%) | 20 |
| Haemoptysis | 21/278 (7.6%) | 21 | 26/280 (9.3%) | 37 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 128/278 (46%) | 128 | 102/280 (36.4%) | 102 |
| Pruritus | 36/278 (12.9%) | 40 | 21/280 (7.5%) | 25 |
| Rash | 39/278 (14%) | 47 | 28/280 (10%) | 32 |
| Vascular disorders | ||||
| Hypotension | 11/278 (4%) | 12 | 15/280 (5.4%) | 16 |
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.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme LLC |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier:
NCT02775435
Other Study ID Numbers:
- 3475-407
- 173568
- MK-3475-407
- KEYNOTE-407
- 2016-000229-38
First Posted:
May 17, 2016
Last Update Posted:
Aug 19, 2022
Last Verified:
Aug 1, 2022