Study of Pembrolizumab Versus Docetaxel in Participants Previously Treated for Non-Small Cell Lung Cancer (MK-3475-033/KEYNOTE-033)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02864394
• Collaborator: (none)
• Enrollment: 425
• Arms: 2
• Anticipated Duration (Months): 73.2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy of pembrolizumab (MK-3475) versus docetaxel in participants with non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) positive tumors who have experienced disease progression after platinum-containing systemic therapy. The primary hypotheses of this study are that pembrolizumab (MK-3475) prolongs overall survival (OS) and that pembrolizumab prolongs progression-free survival (PFS), compared to docetaxel in participants with PD-L1 positive tumors.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Biological: Pembrolizumab; Drug: Docetaxel	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 425 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multinational, Multicenter, Phase III, Randomized Open-label Trial of Pembrolizumab Versus Docetaxel in Previously Treated Subjects With Non-Small Cell Lung Cancer
• Actual Study Start Date: Sep 7, 2016
• Actual Primary Completion Date: Sep 9, 2019
• Anticipated Study Completion Date: Oct 14, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Biological: Pembrolizumab; Pembrolizumab administered IV at 2 mg/kg on Day 1 of each 21-day cycle for up to 35 doses (approximately 24 months).; Other Names: KEYTRUDA® MK-3475
Experimental: Docetaxel Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.	Drug: Docetaxel; Docetaxel administered IV at 75 mg/m^2 on Day 1 of each 21-day cycle as per the approved product label.; Other Names: TAXOTERE®

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors [Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)]

   OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

2. OS in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) [Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)]

   OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

3. Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With PD-L1 Positive (TPS ≥50%) Tumors [Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)]

   PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

4. PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) [Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)]

   PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

Secondary Outcome Measures

1. Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors [Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)]

   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: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥50% stratum of PD-L1 expression.

2. ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) [Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)]

   ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

3. Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors [Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)]

   For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.

4. DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants) [Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)]

   For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).

5. Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 29 months]

   An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants who experienced an AE was reported by treatment arm for all participants (TPS ≥1% stratum of PD-L1 expression) as part of the pre-specified secondary safety analysis (Final Analysis cut-off date of 09-Sep-2019).

6. Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 26 months]

   An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants who discontinued study treatment due to an AE was reported by treatment arm for all participants (TPS ≥1% stratum of PD-L1 expression) as part of the pre-specified secondary safety analysis (Final Analysis cut-off date of 09-Sep-2019).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Chinese participants must be born, raised, and reside in China

• Has a histologically or cytologically confirmed diagnosis of stage IIIB/IV or recurrent NSCLC and have at least one measurable lesion as defined by RECIST 1.1

• Has a life expectancy of ≥3 months

• Has progression of disease (investigator determined) per RECIST 1.1 after treatment with at least two cycles of a platinum-containing doublet

• Has documentation of epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation status

• Participants with an EGFR sensitizing mutation tumor will be excluded

• Has Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 within 10 days prior to study start

• Has provided archival tumor tissue sample or newly obtained formalin fixed tumor tissue from a recent biopsy of a tumor lesion not previously irradiated

• Has a PD-L1 positive tumor as determined by immunohistochemistry at a central laboratory

• Has resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia)

• Has recovered from the toxicity and/or complications of any recent major surgery or radiation therapy

• Females must not be pregnant (negative urine or serum human chorionic gonadotropin test within 72 hours prior to receiving the first dose of study medication)

• Female and male participants of reproductive potential must agree to use adequate contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab (MK-3475) or 180 days after the last dose of docetaxel

Exclusion Criteria:

• Has received prior therapy with docetaxel for NSCLC

• Is currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study treatment

• Is receiving systemic steroid therapy within 3 days prior to the first dose of study treatment or receiving any other form of immunosuppressive

• Is expected to require any other form of systemic or localized antineoplastic therapy while on study including maintenance therapy with another agent for NSCLC or radiation therapy

• Has received prior systemic cytotoxic chemotherapy, antineoplastic biological therapy (e.g., cetuximab), any other agents used as systemic treatment for cancer, or major surgery within 3 weeks of the first dose of study treatment; received thoracic radiation therapy of > 30 Gray Units (Gy) within 6 months of the first dose of study treatment; received prior ALK-directed tyrosine kinase inhibitor therapy or completed palliative radiotherapy of 30 Gy or less within 7 days of the first dose of study treatment

• Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD-L1, anti-PD-L2, with an agent directed to an agonist or antagonist T-cell check point receptor, or if the participant has previously participated in Merck sponsored clinical trials evaluating pembrolizumab (MK-3475)

• Has a known additional malignancy that is progressing or requires active treatment, with the exception of early stage cancers, treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy

• Has known active central nervous system metastases and/or carcinomatous meningitis

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

• Has had an allogeneic tissue/solid organ transplant

• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

• Has received or will receive a live vaccine within 30 days prior to the first administration of study medication

• Has an active infection requiring intravenous systemic therapy

• Has known history of Human Immunodeficiency Virus (HIV) (HIV ½ antibodies)

• Has known active Hepatitis B or C

• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

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

• Is pregnant or breastfeeding, or expecting to conceive or father children starting with the screening visit (Visit 1) through 120 days after the last dose of pembrolizumab (MK-3475) or 180 days after the last dose of docetaxel

• Requires treatment with a strong inhibitor of Cytochrome P450 3A4

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)

• Study Protocol and Statistical Analysis Plan - Oct 1, 2018

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02864394
• Other Study ID Numbers: 3475-033; MK-3475-033; KEYNOTE-033
• First Posted: Aug 12, 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: No
• 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: Carcinoma, Non-Small-Cell Lung; Docetaxel; Pembrolizumab

Study Results

Participant Flow

Recruitment Details	Participants with non-small cell lung cancer (NSCLC) and programmed cell death ligand 1 (PD-L1) positive (Tumor Proportion Score [TPS] ≥1%) tumors who had experienced disease progression after platinum-containing systemic therapy were recruited.
Pre-assignment Detail	Of 425 participants randomized, 411 received treatment on study. All 425 participants were PD-L1 positive (TPS ≥1%). At the time of the Final Analysis data cut-off (09-Sep-2019), 130 participants were ongoing in the study.

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Period Title: Overall Study
STARTED	213	212
Treated	213	198
COMPLETED	0	0
NOT COMPLETED	213	212

Baseline Characteristics

Arm/Group Title	Pembrolizumab	Docetaxel	Total
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.	Total of all reporting groups
Overall Participants	213	212	425
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.6 (8.8)	61.0 (9.2)	60.8 (9.0)
Sex: Female, Male (Count of Participants)
Female	56 26.3%	48 22.6%	104 24.5%
Male	157 73.7%	164 77.4%	321 75.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 7%	14 6.6%	29 6.8%
Not Hispanic or Latino	198 93%	198 93.4%	396 93.2%
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	181 85%	177 83.5%	358 84.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	32 15%	35 16.5%	67 15.8%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
PD-L1 Status (Count of Participants)
TPS ≥50%	114 53.5%	112 52.8%	226 53.2%
TPS = 1-49%	98 46%	98 46.2%	196 46.1%
TPS <1%	0 0%	2 0.9%	2 0.5%
NOT EVALUABLE	1 0.5%	0 0%	1 0.2%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) in Participants With Programmed Cell Death Ligand 1 (PD-L1) Positive (Tumor Proportion Score [TPS] ≥50%) Tumors
Description	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.
Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 TPS ≥50%

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	114	113
Median (95% Confidence Interval) [Months]	12.3	10.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Docetaxel
	Comments	Treatment comparison (Hazard Ratio, HR) based on Cox regression model with Efron's method of tie handling with treatment as a covariate. One-sided p-value was based on log-rank test.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1276
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.61 to 1.14
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	OS in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
Description	OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. Per protocol, OS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).
Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 TPS ≥1% (all participants).

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	213	212
Median (95% Confidence Interval) [Months]	12.9	10.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Docetaxel
	Comments	OS was not formally tested. Treatment comparison (HR) based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by PD-L1 expression status (TPS ≥50% vs. TPS 1-49%). A nominal one-sided p-value for testing was based on log-rank test stratified by PD-L1 expression status (TPS ≥50% vs. TPS 1-49%).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0076
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; 0.60 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With PD-L1 Positive (TPS ≥50%) Tumors
Description	PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters (SOD) of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.
Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 TPS ≥50%

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	114	113
Median (95% Confidence Interval) [Months]	4.0	2.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Docetaxel
	Comments	PFS was not formally tested. Treatment comparison (HR) based on Cox regression model with Efron's method of tie handling with treatment as a covariate. A nominal one-sided p-value for testing was based on log-rank test.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0534
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.76
	Confidence Interval	(2-Sided) 95%; 0.54 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	PFS Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
Description	PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the SOD of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, PFS was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).
Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 TPS ≥1% (all participants).

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	213	212
Median (95% Confidence Interval) [Months]	3.3	3.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Docetaxel
	Comments	PFS was not formally tested. Treatment comparison (HR) based on Cox regression model with Efron's method of tie handling with treatment as a covariate stratified by PD-L1 expression status (TPS ≥50% vs. TPS 1-49%). A nominal one-sided p-value for testing was based on log-rank test stratified by PD-L1 expression status (TPS ≥50% vs. TPS 1-49%).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0847
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95%; 0.66 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors
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: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥50% stratum of PD-L1 expression.
Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 TPS ≥50%

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	114	113
Number (95% Confidence Interval) [Percentage of Participants]	28.1 13.2%	7.1 3.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Docetaxel
	Comments	ORR was not formally tested. Treatment comparison was based on the Miettinen & Nurminen method. A nominal one-sided p-value for testing was calculated.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Miettinen & Nurminen Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	21.0
	Confidence Interval	(2-Sided) 95%; 11.5 to 30.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	ORR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
Description	ORR was defined as the percentage of participants in the analysis population who had a CR (disappearance of all target lesions) or a PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. as assessed by BICR. Per protocol, the percentage of participants who experienced CR or PR is reported here as the ORR for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).
Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Outcome Measure Data

Analysis Population Description

All randomized participants with PD-L1 TPS ≥1% (all participants).

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	213	212
Number (95% Confidence Interval) [Percentage of Participants]	20.7 9.7%	5.7 2.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab, Docetaxel
	Comments	ORR was not formally tested. Treatment comparison was based on Miettinen & Nurminen method stratified by PD-L1 expression status (TPS>=50% vs. TPS 1-49%). If no participants were in one of the treatment arms involved in a comparison for a particular stratum, then that stratum was excluded from the treatment comparison. A nominal one-sided p-value for testing was calculated.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Miettinen & Nurminen Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	15.0
	Confidence Interval	(2-Sided) 95%; 8.8 to 21.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥50%) Tumors
Description	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR was reported by treatment arm for participants in the TPS ≥50% stratum of PD-L1 expression.
Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Outcome Measure Data

Analysis Population Description

All randomized participants in the PD-L1 TPS ≥50% stratum who demonstrated a confirmed CR or PR.

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	32	8
Median (Full Range) [Months]	NA	NA

8. Secondary Outcome

Title	DOR Per RECIST 1.1 as Assessed by BICR in Participants With PD-L1 Positive (TPS ≥1%) Tumors (All Participants)
Description	For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Per protocol, DOR was reported by treatment arm for participants in the TPS ≥1% stratum of PD-L1 expression (all participants).
Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)

Outcome Measure Data

Analysis Population Description

All randomized participants in the PD-L1 TPS ≥1% stratum who demonstrated a confirmed CR or PR.

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	44	12
Median (Full Range) [Months]	NA	NA

9. 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 a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants who experienced an AE was reported by treatment arm for all participants (TPS ≥1% stratum of PD-L1 expression) as part of the pre-specified secondary safety analysis (Final Analysis cut-off date of 09-Sep-2019).
Time Frame	Up to approximately 29 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study treatment.

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	213	198
Count of Participants [Participants]	206 96.7%	187 88.2%

10. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an AE
Description	An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants who discontinued study treatment due to an AE was reported by treatment arm for all participants (TPS ≥1% stratum of PD-L1 expression) as part of the pre-specified secondary safety analysis (Final Analysis cut-off date of 09-Sep-2019).
Time Frame	Up to approximately 26 months

Outcome Measure Data

Analysis Population Description

All randomized participants who received at least one dose of study treatment.

Arm/Group Title	Pembrolizumab	Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes every 3 weeks (Q3W) for up to 35 doses (approximately 24 months).	Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
Measure Participants	213	198
Count of Participants [Participants]	29 13.6%	24 11.3%

Adverse Events

Time Frame	Up to approximately 36 months (through Final Analysis cut-off date of 09-Sep-2019)
Adverse Event Reporting Description	All-Cause Mortality table includes all randomized participants. Serious and Other AEs include all randomized participants who received ≥1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug were excluded as AEs.
Arm/Group Title	Pembrolizumab		Docetaxel
Arm/Group Description	Participants with NSCLC receive pembrolizumab 2 mg/kg intravenously (IV) over 30 minutes Q3W for up to 35 doses (approximately 24 months).		Participants with NSCLC receive Docetaxel 75 mg/m^2 IV over 1 hour Q3W until disease progression, toxicity, investigator's decision to discontinue, or consent withdrawal.
All Cause Mortality
	Pembrolizumab		Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	136/213 (63.8%)		155/212 (73.1%)
Serious Adverse Events
	Pembrolizumab		Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/213 (35.2%)		75/198 (37.9%)
Blood and lymphatic system disorders
Anaemia	2/213 (0.9%)	2	1/198 (0.5%)	1
Coagulopathy	0/213 (0%)	0	1/198 (0.5%)	1
Disseminated intravascular coagulation	1/213 (0.5%)	1	0/198 (0%)	0
Febrile neutropenia	1/213 (0.5%)	1	16/198 (8.1%)	17
Leukopenia	0/213 (0%)	0	3/198 (1.5%)	6
Neutropenia	0/213 (0%)	0	13/198 (6.6%)	21
Thrombocytopenia	2/213 (0.9%)	2	0/198 (0%)	0
Cardiac disorders
Atrial fibrillation	1/213 (0.5%)	1	0/198 (0%)	0
Cardiac failure	1/213 (0.5%)	1	0/198 (0%)	0
Cardiac failure acute	1/213 (0.5%)	1	0/198 (0%)	0
Endocrine disorders
Hypothyroidism	1/213 (0.5%)	1	0/198 (0%)	0
Gastrointestinal disorders
Diarrhoea	0/213 (0%)	0	2/198 (1%)	2
Dysphagia	2/213 (0.9%)	2	0/198 (0%)	0
Gastrointestinal haemorrhage	1/213 (0.5%)	1	0/198 (0%)	0
Nausea	0/213 (0%)	0	1/198 (0.5%)	1
Oesophageal pain	0/213 (0%)	0	1/198 (0.5%)	1
Upper gastrointestinal haemorrhage	1/213 (0.5%)	1	2/198 (1%)	2
Vomiting	1/213 (0.5%)	1	1/198 (0.5%)	1
General disorders
Asthenia	1/213 (0.5%)	1	0/198 (0%)	0
Death	3/213 (1.4%)	3	0/198 (0%)	0
Fatigue	1/213 (0.5%)	1	3/198 (1.5%)	3
Malaise	0/213 (0%)	0	1/198 (0.5%)	1
Multiple organ dysfunction syndrome	0/213 (0%)	0	1/198 (0.5%)	1
Oedema peripheral	1/213 (0.5%)	1	0/198 (0%)	0
Pyrexia	4/213 (1.9%)	4	1/198 (0.5%)	1
Hepatobiliary disorders
Autoimmune hepatitis	1/213 (0.5%)	1	0/198 (0%)	0
Cholecystitis	1/213 (0.5%)	1	0/198 (0%)	0
Hepatic function abnormal	0/213 (0%)	0	1/198 (0.5%)	1
Hyperbilirubinaemia	1/213 (0.5%)	3	0/198 (0%)	0
Immune-mediated hepatitis	3/213 (1.4%)	3	0/198 (0%)	0
Infections and infestations
Appendicitis	2/213 (0.9%)	2	0/198 (0%)	0
Endocarditis	1/213 (0.5%)	1	0/198 (0%)	0
Infected dermal cyst	0/213 (0%)	0	1/198 (0.5%)	1
Lower respiratory tract infection	1/213 (0.5%)	1	0/198 (0%)	0
Lung infection	8/213 (3.8%)	8	9/198 (4.5%)	11
Nasopharyngitis	0/213 (0%)	0	1/198 (0.5%)	1
Paratyphoid fever	0/213 (0%)	0	1/198 (0.5%)	1
Pneumonia	15/213 (7%)	16	10/198 (5.1%)	10
Pulmonary sepsis	0/213 (0%)	0	1/198 (0.5%)	1
Respiratory tract infection	0/213 (0%)	0	1/198 (0.5%)	1
Respiratory tract infection viral	0/213 (0%)	0	1/198 (0.5%)	1
Tracheobronchitis	0/213 (0%)	0	1/198 (0.5%)	2
Upper respiratory tract infection	3/213 (1.4%)	3	3/198 (1.5%)	3
Urinary tract infection	1/213 (0.5%)	1	0/198 (0%)	0
Injury, poisoning and procedural complications
Infusion related reaction	1/213 (0.5%)	1	2/198 (1%)	2
Investigations
Alanine aminotransferase increased	1/213 (0.5%)	1	0/198 (0%)	0
Myocardial necrosis marker increased	1/213 (0.5%)	1	0/198 (0%)	0
Neutrophil count decreased	0/213 (0%)	0	1/198 (0.5%)	1
White blood cell count decreased	0/213 (0%)	0	1/198 (0.5%)	1
Metabolism and nutrition disorders
Decreased appetite	0/213 (0%)	0	2/198 (1%)	2
Dehydration	0/213 (0%)	0	1/198 (0.5%)	1
Diabetes mellitus	1/213 (0.5%)	1	0/198 (0%)	0
Hypercalcaemia	2/213 (0.9%)	2	0/198 (0%)	0
Hyperglycaemia	0/213 (0%)	0	1/198 (0.5%)	1
Hyperuricaemia	1/213 (0.5%)	3	1/198 (0.5%)	2
Hypoalbuminaemia	1/213 (0.5%)	1	0/198 (0%)	0
Hypokalaemia	1/213 (0.5%)	1	0/198 (0%)	0
Malnutrition	2/213 (0.9%)	2	1/198 (0.5%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/213 (0.5%)	1	0/198 (0%)	0
Bone pain	2/213 (0.9%)	3	0/198 (0%)	0
Myositis	1/213 (0.5%)	1	0/198 (0%)	0
Spondylolisthesis	1/213 (0.5%)	1	0/198 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain	1/213 (0.5%)	1	0/198 (0%)	0
Colorectal cancer	0/213 (0%)	0	1/198 (0.5%)	1
Gastrointestinal tract adenoma	0/213 (0%)	0	1/198 (0.5%)	1
Nervous system disorders
Cerebellar infarction	0/213 (0%)	0	1/198 (0.5%)	1
Cerebral infarction	1/213 (0.5%)	2	0/198 (0%)	0
Dizziness	1/213 (0.5%)	1	0/198 (0%)	0
Hypoglossal nerve paralysis	0/213 (0%)	0	1/198 (0.5%)	1
Seizure	0/213 (0%)	0	1/198 (0.5%)	1
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/213 (0%)	0	1/198 (0.5%)	1
Respiratory, thoracic and mediastinal disorders
Asphyxia	0/213 (0%)	0	1/198 (0.5%)	1
Atelectasis	1/213 (0.5%)	1	1/198 (0.5%)	1
Chronic obstructive pulmonary disease	0/213 (0%)	0	2/198 (1%)	2
Cough	1/213 (0.5%)	1	2/198 (1%)	2
Dyspnoea	1/213 (0.5%)	1	3/198 (1.5%)	3
Haemoptysis	3/213 (1.4%)	4	2/198 (1%)	2
Interstitial lung disease	4/213 (1.9%)	4	2/198 (1%)	2
Nasal polyps	1/213 (0.5%)	1	0/198 (0%)	0
Pleural effusion	4/213 (1.9%)	4	0/198 (0%)	0
Pneumonitis	10/213 (4.7%)	10	0/198 (0%)	0
Pneumothorax	0/213 (0%)	0	2/198 (1%)	2
Productive cough	1/213 (0.5%)	1	0/198 (0%)	0
Pulmonary embolism	4/213 (1.9%)	4	1/198 (0.5%)	1
Respiratory distress	1/213 (0.5%)	1	0/198 (0%)	0
Skin and subcutaneous tissue disorders
Skin ulcer	1/213 (0.5%)	1	0/198 (0%)	0
Vascular disorders
Deep vein thrombosis	1/213 (0.5%)	1	0/198 (0%)	0
Venous thrombosis limb	1/213 (0.5%)	1	0/198 (0%)	0
Other (Not Including Serious) Adverse Events
	Pembrolizumab		Docetaxel
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	192/213 (90.1%)		182/198 (91.9%)
Blood and lymphatic system disorders
Anaemia	69/213 (32.4%)	97	93/198 (47%)	150
Leukopenia	5/213 (2.3%)	8	35/198 (17.7%)	65
Neutropenia	1/213 (0.5%)	3	47/198 (23.7%)	82
Endocrine disorders
Hyperthyroidism	20/213 (9.4%)	20	0/198 (0%)	0
Hypothyroidism	27/213 (12.7%)	36	2/198 (1%)	4
Gastrointestinal disorders
Constipation	22/213 (10.3%)	24	25/198 (12.6%)	31
Diarrhoea	18/213 (8.5%)	25	32/198 (16.2%)	43
Nausea	12/213 (5.6%)	13	35/198 (17.7%)	83
Vomiting	14/213 (6.6%)	20	20/198 (10.1%)	29
General disorders
Asthenia	20/213 (9.4%)	20	31/198 (15.7%)	38
Chest pain	27/213 (12.7%)	34	16/198 (8.1%)	17
Fatigue	22/213 (10.3%)	24	36/198 (18.2%)	41
Malaise	14/213 (6.6%)	16	8/198 (4%)	11
Oedema peripheral	7/213 (3.3%)	7	19/198 (9.6%)	25
Pyrexia	21/213 (9.9%)	31	21/198 (10.6%)	25
Infections and infestations
Pneumonia	14/213 (6.6%)	15	9/198 (4.5%)	9
Upper respiratory tract infection	17/213 (8%)	23	5/198 (2.5%)	6
Investigations
Alanine aminotransferase increased	38/213 (17.8%)	52	15/198 (7.6%)	19
Aspartate aminotransferase increased	45/213 (21.1%)	60	14/198 (7.1%)	16
Blood alkaline phosphatase increased	21/213 (9.9%)	22	4/198 (2%)	4
Blood bilirubin increased	16/213 (7.5%)	27	5/198 (2.5%)	9
Blood cholesterol increased	19/213 (8.9%)	29	13/198 (6.6%)	14
Blood creatinine increased	13/213 (6.1%)	24	4/198 (2%)	4
Blood triglycerides increased	12/213 (5.6%)	33	9/198 (4.5%)	19
Gamma-glutamyltransferase increased	21/213 (9.9%)	29	2/198 (1%)	2
Neutrophil count decreased	6/213 (2.8%)	6	28/198 (14.1%)	84
Weight decreased	44/213 (20.7%)	51	25/198 (12.6%)	26
White blood cell count decreased	5/213 (2.3%)	5	54/198 (27.3%)	130
Metabolism and nutrition disorders
Decreased appetite	42/213 (19.7%)	50	51/198 (25.8%)	63
Hyperglycaemia	20/213 (9.4%)	31	9/198 (4.5%)	13
Hypertriglyceridaemia	17/213 (8%)	29	8/198 (4%)	9
Hyperuricaemia	11/213 (5.2%)	24	6/198 (3%)	7
Hypoalbuminaemia	45/213 (21.1%)	56	38/198 (19.2%)	45
Hypocalcaemia	11/213 (5.2%)	14	4/198 (2%)	4
Hypokalaemia	26/213 (12.2%)	35	18/198 (9.1%)	23
Hyponatraemia	25/213 (11.7%)	30	15/198 (7.6%)	19
Hypophosphataemia	13/213 (6.1%)	23	4/198 (2%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	12/213 (5.6%)	15	11/198 (5.6%)	19
Back pain	18/213 (8.5%)	26	18/198 (9.1%)	19
Musculoskeletal pain	12/213 (5.6%)	14	8/198 (4%)	8
Myalgia	8/213 (3.8%)	10	11/198 (5.6%)	18
Pain in extremity	15/213 (7%)	16	16/198 (8.1%)	21
Nervous system disorders
Headache	5/213 (2.3%)	6	13/198 (6.6%)	14
Psychiatric disorders
Insomnia	28/213 (13.1%)	32	24/198 (12.1%)	31
Respiratory, thoracic and mediastinal disorders
Cough	44/213 (20.7%)	54	29/198 (14.6%)	30
Dyspnoea	37/213 (17.4%)	44	32/198 (16.2%)	38
Haemoptysis	34/213 (16%)	53	19/198 (9.6%)	24
Productive cough	17/213 (8%)	18	10/198 (5.1%)	11
Skin and subcutaneous tissue disorders
Alopecia	2/213 (0.9%)	2	93/198 (47%)	97
Pruritus	21/213 (9.9%)	24	5/198 (2.5%)	8
Rash	34/213 (16%)	53	14/198 (7.1%)	17

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.