Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (MK-3475-355/KEYNOTE-355)

Sponsor

Merck Sharp & Dohme LLC (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT02819518

Collaborator

(none)

882

Enrollment

Arms

87.6

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The study will consist of two parts.

In Part 1, the safety of pembrolizumab (MK-3475) in combination with one of three different chemotherapies will be assessed in the treatment of locally recurrent inoperable or metastatic triple negative breast cancer (TNBC), which has not been previously treated with chemotherapy.

In Part 2, the safety and efficacy of pembrolizumab plus background chemotherapy will be assessed compared to the safety and efficacy of placebo plus background chemotherapy in the treatment of locally recurrent inoperable or metastatic TNBC, which has not been previously treated with chemotherapy.

The primary hypotheses are that:

the combination of pembrolizumab and chemotherapy prolongs Progression-Free Survival (PFS) compared to placebo and chemotherapy in:

all participants,
participants with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 tumors, and
participants with PD-L1 CPS ≥10 tumors, and

the combination of pembrolizumab and chemotherapy prolongs Overall Survival (OS) compared to placebo and chemotherapy in:

all participants,
participants with PD-L1 CPS ≥1 tumors, and
participants with PD-L1 CPS ≥10 tumors.

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Cancer (TNBC)	Biological: Pembrolizumab Drug: Nab-paclitaxel Drug: Paclitaxel Drug: Gemcitabine Drug: Carboplatin Drug: Normale Saline Solution	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

882 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-Blind, Phase III Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer - (KEYNOTE-355)

Actual Study Start Date :

Jul 27, 2016

Actual Primary Completion Date :

Jun 15, 2021

Anticipated Study Completion Date :

Nov 15, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Pembrolizumab + Nab-paclitaxel Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Biological: Pembrolizumab IV infusion Other Names: MK-3475 KEYTRUDA® Drug: Nab-paclitaxel IV infusion Other Names: ABRAXANE®
Experimental: Part 1: Pembrolizumab + Paclitaxel Participants receive pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Biological: Pembrolizumab IV infusion Other Names: MK-3475 KEYTRUDA® Drug: Paclitaxel IV infusion Other Names: TAXOL®
Experimental: Part 1: Pembrolizumab + Gemcitabine/Carboplatin Participants receive pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Biological: Pembrolizumab IV infusion Other Names: MK-3475 KEYTRUDA® Drug: Gemcitabine IV infusion Other Names: GEMZAR® Drug: Carboplatin IV infusion Other Names: PARAPLATIN®
Experimental: Part 2: Pembrolizumab + Chemotherapy Participants receive pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Biological: Pembrolizumab IV infusion Other Names: MK-3475 KEYTRUDA® Drug: Nab-paclitaxel IV infusion Other Names: ABRAXANE® Drug: Paclitaxel IV infusion Other Names: TAXOL® Drug: Gemcitabine IV infusion Other Names: GEMZAR® Drug: Carboplatin IV infusion Other Names: PARAPLATIN®
Active Comparator: Part 2: Placebo + Chemotherapy Participants receive placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Drug: Nab-paclitaxel IV infusion Other Names: ABRAXANE® Drug: Paclitaxel IV infusion Other Names: TAXOL® Drug: Gemcitabine IV infusion Other Names: GEMZAR® Drug: Carboplatin IV infusion Other Names: PARAPLATIN® Drug: Normale Saline Solution IV infusion

Outcome Measures

Primary Outcome Measures

Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants [Up to approximately 39 months]
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants [Up to approximately 39 months]
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Part 2: Progression-Free Survival (PFS) - All Participants [Up to approximately 53 months]
Progression-free survival was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on assessments by blinded independent central review (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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors [Up to approximately 53 months]
Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors [Up to approximately 53 months]
Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Part 2: Overall Survival (OS) - All Participants [Up to approximately 53 months]
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors [Up to approximately 53 months]
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors [Up to approximately 53 months]
Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.

Secondary Outcome Measures

Part 2: Objective Response Rate (ORR) - All Participants [Up to approximately 53 months]
Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors [Up to approximately 53 months]
Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors [Up to approximately 53 months]
Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Part 2: Duration of Response (DOR) - All Participants [Up to approximately 53 months]
For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. 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 must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors [Up to approximately 53 months]
For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. 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 must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors [Up to approximately 53 months]
For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. 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 must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Part 2: Disease Control Rate (DCR) - All Participants [Up to approximately 53 months]
Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors [Up to approximately 53 months]
Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors [Up to approximately 53 months]
Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Part 2: Percentage of Participants Who Experienced an AE- All Participants [Up to approximately 53 months]
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants [Up to approximately 52 months]
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants [Baseline and Week 15]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors [Baseline and Week 15]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors [Baseline and Week 15]
The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants [Baseline and Week 15]
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 Tumors [Baseline and Week 15]
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 Tumors [Baseline and Week 15]
EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Has locally recurrent inoperable breast cancer not previously treated with chemotherapy and which cannot be treated with curative intent OR has metastatic breast cancer not previously treated with chemotherapy.
Has centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology/college of American Pathologists (ASCO/CAP) guidelines.
Has completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months elapsed between the completion of treatment with curative intent (e.g., date of primary breast tumor surgery or date of last adjuvant chemotherapy administration, whichever occurred last) and first documented local or distant disease recurrence.
Has been treated with (neo)adjuvant anthracycline, if they received systemic treatment in the (neo)adjuvant setting, unless anthracycline was contraindicated or not considered the best treatment option for the participant in the opinion of the treating physician.
Has measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by local radiology review.
Has provided recently or newly obtained core or excisional biopsy from a locally recurrent inoperable or metastatic tumor lesion for central determination of TNBC status and PD-L1 expression, unless contraindicated due to site inaccessibility and/or participant safety concerns.
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to the start of study drug.
Has a life expectancy ≥12 weeks from randomization.
Demonstrates adequate organ function, within 10 days prior to the start of study drug.
Female participants are eligible to participate if they are not pregnant or breastfeeding AND they are not a woman of childbearing potential (WOCBP) OR is a WOCBP using a contraceptive method that is highly effective or is abstinent from heterosexual intercourse during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention AND has a negative highly-sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours (urine) or 72 hours (serum) before the first dose of study intervention.
Male participants are eligible to participate if they agree to refrain from donating sperm during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention PLUS be abstinent from heterosexual intercourse OR must agree to use contraception unless confirmed to be azoospermic.

Exclusion Criteria:

Is currently participating in a clinical study and receiving an investigational agent and/or using an investigational device, or has participated in a clinical study and received an investigational agent and/or used an investigational device within 4 weeks prior to randomization.
Has not recovered (e.g., to ≤ Grade 1 or to baseline) from AEs due to a previously administered therapy.
Has neuropathy ≥ Grade 2.
Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable brain metastases and did not receive chemotherapy for metastatic breast cancer.
Has history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
Has active, or a history of, interstitial lung disease.
Has a known history of active tuberculosis (TB).
Has an active infection requiring systemic therapy.
Has a history of Class II-IV congestive heart failure or myocardial infarction within 6 months of randomization.
Has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days (or longer as specified by local institutional guidelines) after the last dose of study drug.
Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T cell receptor (such as cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137) or has previously participated in Merck pembrolizumab (MK-3475) clinical studies.
Has a known history of human immunodeficiency virus (HIV).
Has known active hepatitis B or hepatitis C.
Has received a live vaccine within 30 days prior to randomization.
Has a known history of hypersensitivity or allergy to pembrolizumab and any of its components and/or to any of the study chemotherapies (e.g., nab-paclitaxel, paclitaxel, gemcitabine, or carboplatin) and any of their components.
Is receiving any medication prohibited in combination with study chemotherapies as described in the respective product labels, unless medication was stopped within 7 days prior to randomization.

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:

Merck Oncology Clinical Trial Information

Publications

None provided.

Responsible Party:

Merck Sharp & Dohme LLC

ClinicalTrials.gov Identifier:

NCT02819518

Other Study ID Numbers:

3475-355
163422
MK-3475-355
KEYNOTE-355
2016-001432-35

First Posted:

Jun 30, 2016

Last Update Posted:

Jul 25, 2022

Last Verified:

Jul 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by Merck Sharp & Dohme LLC

Programmed Cell Death-1 (PD1, PD-1)

Programmed Cell Death 1 Ligand 1(PDL1, PD-L1)

Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Additional relevant MeSH terms:

Breast Neoplasms

Triple Negative Breast Neoplasms

Gemcitabine

Paclitaxel

Albumin-Bound Paclitaxel

Carboplatin

Pembrolizumab

Study Results

Participant Flow

Recruitment Details

Pre-assignment Detail

35 participants were randomized to Part 1 (Safety Run-in) of the study, and 847 participants were randomized in Part 2 (phase 3) of the study. Eight participants randomized to the Part 2: Pembrolizumab + Chemotherapy arm received a second course of pembrolizumab at the investigator's discretion. Per protocol, response/progression or adverse events (AEs) that occurred during the second course were not counted towards efficacy outcome measures or safety outcome measures respectively.

Arm/Group Title	Part 1: Pembrolizumab + Nab-paclitaxel	Part 1: Pembrolizumab + Paclitaxel	Part 1: Pembrolizumab + Gemcitabine/Carboplatin	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Qualified participants who received first course of pembrolizumab but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to ~1 year).	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle
Period Title: Overall Study
STARTED	11	14	10	566	281
COMPLETED	0	0	0	0	0
NOT COMPLETED	11	14	10	566	281

Baseline Characteristics

Arm/Group Title	Part 1: Pembrolizumab + Nab-paclitaxel	Part 1: Pembrolizumab + Paclitaxel	Part 1: Pembrolizumab + Gemcitabine/Carboplatin	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy	Total
Arm/Group Description	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle. Qualified participants who received first course of pembrolizumab but continued to experience disease progression may have, at investigator's discretion, initiated a second course of pembrolizumab at 200 mg IV Q3W for up to 17 administrations (up to ~1 year).	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Total of all reporting groups
Overall Participants	11	14	10	566	281	882
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.6 (13.5)	60.4 (15.3)	59.6 (11.7)	53.5 (12.7)	53.0 (12.7)	53.5 (12.8)
Sex: Female, Male (Count of Participants)
Female	11 100%	14 100%	10 100%	566 100%	281 100%	882 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 9.1%	0 0%	0 0%	116 20.5%	48 17.1%	165 18.7%
Not Hispanic or Latino	9 81.8%	14 100%	10 100%	423 74.7%	218 77.6%	674 76.4%
Unknown or Not Reported	1 9.1%	0 0%	0 0%	27 4.8%	15 5.3%	43 4.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	11 1.9%	1 0.4%	12 1.4%
Asian	4 36.4%	7 50%	4 40%	123 21.7%	52 18.5%	190 21.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 9.1%	0 0%	0 0%	20 3.5%	17 6%	38 4.3%
White	6 54.5%	7 50%	6 60%	384 67.8%	195 69.4%	598 67.8%
More than one race	0 0%	0 0%	0 0%	11 1.9%	8 2.8%	19 2.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	17 3%	8 2.8%	25 2.8%
Programmed Cell Death Ligand 1 (PD-L1) Status (Combined Positive Score [CPS] Cutoff of 1) (Count of Participants)
PD-L1 CPS ≥1	8 72.7%	12 85.7%	7 70%	425 75.1%	211 75.1%	663 75.2%
PD-L1 CPS <1	3 27.3%	2 14.3%	3 30%	141 24.9%	70 24.9%	219 24.8%
PD-L1 Status (CPS Cutoff of 10) (Count of Participants)
PD-L1 CPS ≥10	1 9.1%	9 64.3%	4 40%	220 38.9%	103 36.7%	337 38.2%
PD-L1 CPS <10	10 90.9%	5 35.7%	6 60%	346 61.1%	178 63.3%	545 61.8%

Outcome Measures

1. Primary Outcome

Title	Part 1: Percentage of Participants Who Experienced an Adverse Event (AE) - All Participants
Description	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame	Up to approximately 39 months

Outcome Measure Data

Analysis Population Description
All randomly assigned participants who received at least 1 dose of study intervention were included in the group corresponding to the study intervention actually received. Four participants assigned to the pembrolizumab + paclitaxel group received incorrect chemotherapy in error: 3 participants received pembrolizumab + nab-paclitaxel and 1 received pembrolizumab + gemcitabine/carboplatin.

Arm/Group Title	Part 1: Pembrolizumab + Nab-paclitaxel	Part 1: Pembrolizumab + Paclitaxel	Part 1: Pembrolizumab + Gemcitabine/Carboplatin
Arm/Group Description	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	13	10	11
Number [Percentage of Participants]	100.0 909.1%	100.0 714.3%	100.0 1000%

2. Primary Outcome

Title	Part 1: Percentage of Participants Who Discontinued Study Drug Due to an AE - All Participants
Description	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame	Up to approximately 39 months

Outcome Measure Data

Analysis Population Description
All randomly assigned participants who received at least 1 dose of study intervention were included in the group corresponding to the study intervention actually received. Four participants assigned to the pembrolizumab + paclitaxel group received incorrect chemotherapy in error: 3 participants received pembrolizumab + nab-paclitaxel and 1 received pembrolizumab + gemcitabine/carboplatin.

Arm/Group Title	Part 1: Pembrolizumab + Nab-paclitaxel	Part 1: Pembrolizumab + Paclitaxel	Part 1: Pembrolizumab + Gemcitabine/Carboplatin
Arm/Group Description	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	13	10	11
Number [Percentage of Participants]	38.5 350%	50.0 357.1%	27.3 273%

3. Primary Outcome

Title	Part 2: Progression-Free Survival (PFS) - All Participants
Description	Progression-free survival was defined as the time from randomization to the first documented progressive disease (PD) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) based on assessments by blinded independent central review (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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	566	281
Median (95% Confidence Interval) [Months]	7.5	5.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0120
	Comments	One-sided p-value based on log-rank test stratified by chemotherapy (taxane versus [vs] gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs. no).
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.82
	Confidence Interval	(2-Sided) 95% 0.70 to 0.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.

4. Primary Outcome

Title	Part 2: PFS - Participants With Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors
Description	Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	425	211
Median (95% Confidence Interval) [Months]	7.6	5.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0016
	Comments	One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95% 0.62 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.

5. Primary Outcome

Title	Part 2: PFS - Participants With PD-L1 CPS ≥10 Tumors
Description	Progression-free survival was defined as the time from randomization to the first documented PD per RECIST 1.1 based on assessments by 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 of target lesions. In addition to the relative increase of 20%, the sum must also have demonstrated an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	220	103
Median (95% Confidence Interval) [Months]	9.7	5.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0018
	Comments	One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95% 0.50 to 0.88
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.

6. Primary Outcome

Title	Part 2: Overall Survival (OS) - All Participants
Description	Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	566	281
Median (95% Confidence Interval) [Months]	17.2	15.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0797
	Comments	One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95% 0.76 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.

7. Primary Outcome

Title	Part 2: OS - Participants With PD-L1 CPS ≥1 Tumors
Description	Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	425	211
Median (95% Confidence Interval) [Months]	17.6	16.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0563
	Comments	One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95% 0.72 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.

8. Primary Outcome

Title	Part 2: OS - Participants With PD-L1 CPS ≥10 Tumors
Description	Overall survival is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the analysis were censored at the date of the last follow-up.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	220	103
Median (95% Confidence Interval) [Months]	23.0	16.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0093
	Comments	One-sided p-value based on log-rank test stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).
	Method	Log Rank
	Comments

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95% 0.55 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by chemotherapy on study, tumor PD-L1 status, and prior treatment with same class of chemotherapy in the (neo)adjuvant setting.

9. Secondary Outcome

Title	Part 2: Objective Response Rate (ORR) - All Participants
Description	Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	566	281
Number (95% Confidence Interval) [Percentage of Participants]	40.8 370.9%	37.0 264.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1413
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Difference in ORR (%) vs. Control
	Estimated Value	3.8
	Confidence Interval	(2-Sided) 95% -3.2 to 10.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).

10. Secondary Outcome

Title	Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors
Description	Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants with PD-L1 CPS ≥1 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	425	211
Number (95% Confidence Interval) [Percentage of Participants]	44.9 408.2%	38.9 277.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0725
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Difference in ORR (%) vs. Control
	Estimated Value	6.1
	Confidence Interval	(2-Sided) 95% -2.1 to 14.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).

11. Secondary Outcome

Title	Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors
Description	Objective response rate is defined as the percentage of participants in the analysis population who have a 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). The percentage of participants who experienced a CR or PR as assessed by BICR based on RECIST 1.1 is presented.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants with PD-L1 CPS ≥10 tumors were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	220	103
Number (95% Confidence Interval) [Percentage of Participants]	52.7 479.1%	40.8 291.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0213
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Difference in ORR(%) vs. Control
	Estimated Value	12.1
	Confidence Interval	(2-Sided) 95% 0.4 to 23.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin) and prior treatment with same class of chemotherapy in the (neo)adjuvant setting (yes vs no).

12. Secondary Outcome

Title	Part 2: Duration of Response (DOR) - All Participants
Description	For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. 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 must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
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	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	231	104
Median (Full Range) [Months]	NA	6.5

13. Secondary Outcome

Title	Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors
Description	For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. 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 must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
All randomized participants with PD-LI CPS ≥1 tumors 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	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	191	82
Median (Full Range) [Months]	NA	6.8

14. Secondary Outcome

Title	Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors
Description	For participants who demonstrate a confirmed CR (Disappearance of all target lesions) or confirmed PR (At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death due to any cause, whichever occurs first, based on assessments by BICR per RECIST 1.1. 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 must also have demonstrated an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered PD.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
All randomized participants with PD-LI CPS ≥10 tumors 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	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	116	42
Median (Full Range) [Months]	NA	7.3

15. Secondary Outcome

Title	Part 2: Disease Control Rate (DCR) - All Participants
Description	Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	566	281
Number (95% Confidence Interval) [Percentage of Participants]	56.0 509.1%	51.2 365.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0966
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Difference in DCR (%) vs. control
	Estimated Value	4.7
	Confidence Interval	(2-Sided) 95% -2.4 to 11.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin), tumor PD-L1 status (CPS ≥1 vs CPS <1) and prior treatment with same class of chemotherapy in the (neo) adjuvant setting (yes vs no).

16. Secondary Outcome

Title	Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors
Description	Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants with PD-L1 CPS ≥1 tumors at baseline were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	425	211
Number (95% Confidence Interval) [Percentage of Participants]	58.6 532.7%	53.6 382.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.1164
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Difference in DCR (%) vs. Control
	Estimated Value	5.0
	Confidence Interval	(2-Sided) 95% -3.2 to 13.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin) and prior treatment with same class of chemotherapy in the (neo) adjuvant setting (yes vs no).

17. Secondary Outcome

Title	Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors
Description	Disease control rate is defined as the percentage of participants who have achieved CR (disappearance of all target lesions) or PR (At least a 30% decrease in the sum of diameters of target lesions) or have demonstrated stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease [PD: At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD]) for at least 24 weeks, based on assessments by BICR per RECIST 1.1.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
Participants with PD-L1 CPS ≥10 tumors at baseline were analyzed in the treatment arm to which they were randomly assigned, regardless of whether they received treatment

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	220	103
Number (95% Confidence Interval) [Percentage of Participants]	65.0 590.9%	54.4 388.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Pembrolizumab + Nab-paclitaxel, Part 1: Pembrolizumab + Paclitaxel
	Comments
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	0.0327
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments

Method of Estimation	Estimation Parameter	Difference in DCR (%) vs. Control
	Estimated Value	10.8
	Confidence Interval	(2-Sided) 95% -0.7 to 22.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Based on Miettinen & Nurminen method stratified by chemotherapy on study (taxane vs gemcitabine/carboplatin) and prior treatment with same class of chemotherapy in the (neo) adjuvant setting (yes vs no).

18. Secondary Outcome

Title	Part 2: Percentage of Participants Who Experienced an AE- All Participants
Description	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame	Up to approximately 53 months

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study intervention. Participants were included in the group corresponding to the study intervention actually received.

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	562	281
Number [Percentage of Participants]	98.6 896.4%	98.2 701.4%

19. Secondary Outcome

Title	Part 2: Percentage of Participants Who Discontinued Study Drug Due to an AE- All Participants
Description	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Time Frame	Up to approximately 52 months

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study intervention. Participants were included in the group corresponding to the study intervention actually received.

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	562	281
Number [Percentage of Participants]	20.5 186.4%	13.5 96.4%

20. Secondary Outcome

Title	Part 2: Change From Baseline to Week 15 in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score- All Participants
Description	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time Frame	Baseline and Week 15

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	554	278
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	-3.52	-2.15

21. Secondary Outcome

Title	Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score - Participants With PD-L1 CPS ≥1 Tumors
Description	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time Frame	Baseline and Week 15

Outcome Measure Data

Analysis Population Description
All randomized participants with PD-L1 CPS ≥1 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	415	208
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	-3.92	-3.15

22. Secondary Outcome

Title	Part 2: Change From Baseline to Week 15 in EORTC QLQ-C30 Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score-Participants With PD-L1 CPS ≥10 Tumors
Description	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" (Item 29) and "How would you rate your overall quality of life during the past week?" (Item 30) were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized, so that scores range from 0 to 100. A higher score indicates a better overall health status. The change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score are presented.
Time Frame	Baseline and Week 15

Outcome Measure Data

Analysis Population Description
All randomized participants with PD-L1 CPS ≥10 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	216	100
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	-2.69	-0.88

23. Secondary Outcome

Title	Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23)-All Participants
Description	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time Frame	Baseline and Week 15

Outcome Measure Data

Analysis Population Description
All randomized participants who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	554	278
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	12.50	12.36

24. Secondary Outcome

Title	Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23 - Participants With PD-L1 CPS ≥1 Tumors
Description	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time Frame	Baseline and Week 15

Outcome Measure Data

Analysis Population Description
All randomized participants with PD-L1 CPS ≥1 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	415	208
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	13.00	11.86

25. Secondary Outcome

Title	Part 2: Change From Baseline to Week 15 in Systemic Therapy Side Effects Using the EORTC QLQ-BR23- Participants With PD-L1 CPS ≥10 Tumors
Description	EORTC-QLQ-BR23 is a 23-item breast cancer-specific companion module to the EORTC-QLQ-C30 and consists of four functional scales (body image, sexual enjoyment, sexual functioning, future perspective) and four symptom scales (systemic therapy side effects, upset by hair loss, arm symptoms, breast symptoms). Participant responses to 7 questions about their systemic therapy side effects are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A higher score denotes worse symptoms for the systemic therapy side effects symptom scale. The change from baseline in systemic therapy side effects (EORTC QLQ-BR23 Items 1-4, 6, 7, and 8) score is presented.
Time Frame	Baseline and Week 15

Outcome Measure Data

Analysis Population Description
All randomized participants with PD-L1 CPS ≥10 tumors who received at least 1 dose of study intervention and had completed at least 1 patient-reported outcome (PRO) assessment. Participants were included in the treatment arm to which they were randomly assigned.

Arm/Group Title	Part 2: Pembrolizumab + Chemotherapy	Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.	Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
Measure Participants	216	100
Least Squares Mean (95% Confidence Interval) [Scores on a scale]	13.56	13.26

Adverse Events

	Part 1: Pembrolizumab + Nab-paclitaxel		Part 1: Pembrolizumab + Paclitaxel		Part 1: Pembrolizumab + Gemcitabine/Carboplatin		Part 2: Pembrolizumab + Chemotherapy (First Course)		Part 2: Pembrolizumab + Chemotherapy (Second Course)		Part 2: Placebo + Chemotherapy
Time Frame	Up to approximately 53 months (database cutoff date: 15JUN2021)
Adverse Event Reporting Description	The population for all cause mortality includes all participants in the treatment arm to which they were randomly assigned. The population for AEs includes all participants who received at least 1 dose of study intervention in the arm of the study intervention received. 4 participants assigned to the Part 1: pembrolizumab + paclitaxel group received incorrect chemotherapy in error: 3 participants received pembrolizumab + nab-paclitaxel and 1 received pembrolizumab + gemcitabine/carboplatin.

Arm/Group Title	Part 1: Pembrolizumab + Nab-paclitaxel		Part 1: Pembrolizumab + Paclitaxel		Part 1: Pembrolizumab + Gemcitabine/Carboplatin		Part 2: Pembrolizumab + Chemotherapy (First Course)		Part 2: Pembrolizumab + Chemotherapy (Second Course)		Part 2: Placebo + Chemotherapy
Arm/Group Description	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.		Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.		Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.		Participants received pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.		Eligible participants received up to 17 additional administrations (up to approximately 1 year) of pembrolizumab 200 mg IV on day 1 of each 21-day cycle.		Participants received placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three background chemotherapy regimens at investigator's discretion: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/11 (81.8%)		11/14 (78.6%)		9/10 (90%)		459/566 (81.1%)		1/8 (12.5%)		238/281 (84.7%)
Serious Adverse Events
	Part 1: Pembrolizumab + Nab-paclitaxel		Part 1: Pembrolizumab + Paclitaxel		Part 1: Pembrolizumab + Gemcitabine/Carboplatin		Part 2: Pembrolizumab + Chemotherapy (First Course)		Part 2: Pembrolizumab + Chemotherapy (Second Course)		Part 2: Placebo + Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/13 (23.1%)		4/10 (40%)		9/11 (81.8%)		169/562 (30.1%)		2/8 (25%)		67/281 (23.8%)
Blood and lymphatic system disorders
Anaemia	0/13 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	3	11/562 (2%)	12	0/8 (0%)	0	6/281 (2.1%)	8
Febrile neutropenia	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	2	7/562 (1.2%)	7	0/8 (0%)	0	3/281 (1.1%)	3
Leukopenia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	6	0/8 (0%)	0	0/281 (0%)	0
Lymphopenia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Myelosuppression	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Neutropenia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	5/562 (0.9%)	7	0/8 (0%)	0	4/281 (1.4%)	4
Pancytopenia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Thrombocytopenia	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	11/562 (2%)	14	0/8 (0%)	0	4/281 (1.4%)	7
Thrombotic microangiopathy	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Cardiac disorders
Acute myocardial infarction	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Arrhythmia	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Atrial fibrillation	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Cardiac arrest	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Cardiac failure	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	1/281 (0.4%)	1
Cardiac failure congestive	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Cardio-respiratory arrest	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Cardiopulmonary failure	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Myocarditis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Sinus bradycardia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Endocrine disorders
Adrenal insufficiency	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	4	0/8 (0%)	0	0/281 (0%)	0
Hypothyroidism	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Inappropriate antidiuretic hormone secretion	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Eye disorders
Papilloedema	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Cheilitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Colitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Diarrhoea	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	4	0/8 (0%)	0	0/281 (0%)	0
Dysphagia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Food poisoning	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Gastric ulcer haemorrhage	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Gastritis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Haematemesis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Intestinal obstruction	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	2	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Intestinal pseudo-obstruction	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Lower gastrointestinal haemorrhage	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Nausea	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	3	0/8 (0%)	0	3/281 (1.1%)	3
Pancreatitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Stomatitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Vomiting	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	10/562 (1.8%)	12	0/8 (0%)	0	6/281 (2.1%)	7
General disorders
Asthenia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	2/281 (0.7%)	2
Chest pain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Death	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Drug withdrawal syndrome	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Face oedema	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Fat necrosis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Fatigue	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Malaise	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	3	0/8 (0%)	0	0/281 (0%)	0
Multiple organ dysfunction syndrome	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Non-cardiac chest pain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Oedema peripheral	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pyrexia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	7/562 (1.2%)	8	0/8 (0%)	0	4/281 (1.4%)	6
Hepatobiliary disorders
Autoimmune hepatitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Hepatic function abnormal	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	1/281 (0.4%)	1
Hepatitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	5	0/8 (0%)	0	0/281 (0%)	0
Hepatotoxicity	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Liver disorder	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Steatohepatitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Immune system disorders
Anaphylactic reaction	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Infections and infestations
Abdominal abscess	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Abscess	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Bacteraemia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Biliary tract infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Breast cellulitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Cellulitis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Cystitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Device related infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Device related sepsis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Gastroenteritis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Herpes zoster	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Influenza	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Lower respiratory tract infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Mastitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	1/8 (12.5%)	1	0/281 (0%)	0
Meningitis aseptic	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Nasopharyngitis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Neutropenic sepsis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pneumocystis jirovecii pneumonia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pneumonia	2/13 (15.4%)	2	0/10 (0%)	0	0/11 (0%)	0	11/562 (2%)	11	0/8 (0%)	0	7/281 (2.5%)	7
Pneumonia bacterial	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pneumonia mycoplasmal	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Pneumonia staphylococcal	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Pneumonia streptococcal	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pseudomonal sepsis	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Pulmonary sepsis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pyelonephritis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Respiratory tract infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Sepsis	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	6/562 (1.1%)	6	0/8 (0%)	0	3/281 (1.1%)	3
Septic shock	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Skin infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Soft tissue infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	3	0/8 (0%)	0	0/281 (0%)	0
Staphylococcal infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Staphylococcal sepsis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Streptococcal sepsis	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Superinfection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Upper respiratory tract infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	1/281 (0.4%)	1
Urinary tract infection	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Urosepsis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Vascular device infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	1/8 (12.5%)	1	1/281 (0.4%)	1
Viral infection	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Ligament sprain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Limb injury	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Lumbar vertebral fracture	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Procedural pneumothorax	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Radius fracture	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	2/281 (0.7%)	2
Rib fracture	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Transfusion reaction	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Transfusion-related acute lung injury	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Traumatic intracranial haemorrhage	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Vascular access complication	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Investigations
Alanine aminotransferase increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	5	0/8 (0%)	0	1/281 (0.4%)	1
Aspartate aminotransferase increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	5	0/8 (0%)	0	1/281 (0.4%)	1
Blood corticotrophin increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	1/8 (12.5%)	1	0/281 (0%)	0
Blood creatinine increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Cortisol decreased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Hepatic enzyme increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Liver function test abnormal	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Neutrophil count decreased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pancreatic enzymes increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Platelet count decreased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	5/562 (0.9%)	6	0/8 (0%)	0	2/281 (0.7%)	2
Transaminases increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	1/281 (0.4%)	1
Dehydration	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Diabetes mellitus	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Diabetes mellitus inadequate control	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Electrolyte imbalance	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Hypercalcaemia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Hypoalbuminaemia	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Hypocalcaemia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	2/281 (0.7%)	2
Hypokalaemia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Hyponatraemia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	2/281 (0.7%)	2
Type 1 diabetes mellitus	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Bone pain	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Musculoskeletal pain	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Myositis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pain in extremity	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pathological fracture	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Polyarthritis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Scleroderma	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Basal cell carcinoma	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Cancer pain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Chronic lymphocytic leukaemia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Endometrial adenocarcinoma	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Tumour haemorrhage	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Tumour necrosis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Tumour pain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Nervous system disorders
Brain oedema	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Cerebellar haemorrhage	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Cerebral haematoma	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Cerebral venous sinus thrombosis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Cerebrovascular accident	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Chronic inflammatory demyelinating polyradiculoneuropathy	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Guillain-Barre syndrome	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Haemorrhagic stroke	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Headache	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	2/281 (0.7%)	2
Hepatic encephalopathy	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	2	0/8 (0%)	0	0/281 (0%)	0
Intracranial pressure increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Myelopathy	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Parkinsonism	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Peripheral motor neuropathy	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Peripheral sensory neuropathy	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	2/281 (0.7%)	2
Syncope	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Transient ischaemic attack	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Product Issues
Device dislocation	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Psychiatric disorders
Anxiety	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Assisted suicide	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Confusional state	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Renal and urinary disorders
Acute kidney injury	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	3	0/8 (0%)	0	1/281 (0.4%)	2
Hydronephrosis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Kidney enlargement	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Nephritis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Renal failure	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Urinary retention	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Urinary tract obstruction	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Reproductive system and breast disorders
Abnormal uterine bleeding	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Breast pain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Uterine haemorrhage	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Bronchostenosis	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Chronic obstructive pulmonary disease	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Dyspnoea	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Obstructive airways disorder	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Pleural effusion	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	5/562 (0.9%)	6	0/8 (0%)	0	3/281 (1.1%)	3
Pleurisy	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pleuritic pain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pneumonia aspiration	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pneumonitis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	6/562 (1.1%)	8	0/8 (0%)	0	0/281 (0%)	0
Pneumothorax	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	2/281 (0.7%)	2
Pulmonary embolism	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	7/562 (1.2%)	7	0/8 (0%)	0	3/281 (1.1%)	3
Pulmonary fibrosis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Pulmonary hypertension	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Respiratory failure	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Skin and subcutaneous tissue disorders
Drug eruption	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Palmar-plantar erythrodysaesthesia syndrome	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Rash maculo-papular	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Subcutaneous emphysema	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Vascular disorders
Deep vein thrombosis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	1/281 (0.4%)	1
Embolism	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Hypertension	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Hypertensive emergency	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Hypotension	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Shock haemorrhagic	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Thrombosis	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Varicose vein	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Venous thrombosis limb	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Other (Not Including Serious) Adverse Events
	Part 1: Pembrolizumab + Nab-paclitaxel		Part 1: Pembrolizumab + Paclitaxel		Part 1: Pembrolizumab + Gemcitabine/Carboplatin		Part 2: Pembrolizumab + Chemotherapy (First Course)		Part 2: Pembrolizumab + Chemotherapy (Second Course)		Part 2: Placebo + Chemotherapy
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/13 (100%)		10/10 (100%)		11/11 (100%)		551/562 (98%)		7/8 (87.5%)		273/281 (97.2%)
Blood and lymphatic system disorders
Anaemia	5/13 (38.5%)	5	5/10 (50%)	15	8/11 (72.7%)	13	294/562 (52.3%)	625	1/8 (12.5%)	3	140/281 (49.8%)	246
Leukopenia	0/13 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	44	111/562 (19.8%)	447	0/8 (0%)	0	50/281 (17.8%)	158
Lymphopenia	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	30/562 (5.3%)	62	0/8 (0%)	0	4/281 (1.4%)	15
Neutropenia	2/13 (15.4%)	3	1/10 (10%)	21	7/11 (63.6%)	67	232/562 (41.3%)	928	1/8 (12.5%)	1	109/281 (38.8%)	377
Thrombocytopenia	0/13 (0%)	0	0/10 (0%)	0	5/11 (45.5%)	63	110/562 (19.6%)	346	0/8 (0%)	0	56/281 (19.9%)	155
Cardiac disorders
Tachycardia	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	8/562 (1.4%)	11	0/8 (0%)	0	3/281 (1.1%)	3
Ear and labyrinth disorders
Vertigo	1/13 (7.7%)	1	1/10 (10%)	1	0/11 (0%)	0	20/562 (3.6%)	22	0/8 (0%)	0	12/281 (4.3%)	13
Endocrine disorders
Adrenal insufficiency	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	4	0/8 (0%)	0	0/281 (0%)	0
Hyperthyroidism	1/13 (7.7%)	1	2/10 (20%)	3	1/11 (9.1%)	1	24/562 (4.3%)	24	0/8 (0%)	0	3/281 (1.1%)	3
Hypophysitis	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Hypothyroidism	1/13 (7.7%)	1	3/10 (30%)	3	4/11 (36.4%)	5	88/562 (15.7%)	100	0/8 (0%)	0	9/281 (3.2%)	10
Thyroiditis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	6/562 (1.1%)	6	0/8 (0%)	0	0/281 (0%)	0
Eye disorders
Diplopia	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	5/281 (1.8%)	5
Dry eye	1/13 (7.7%)	1	0/10 (0%)	0	1/11 (9.1%)	1	20/562 (3.6%)	20	0/8 (0%)	0	8/281 (2.8%)	8
Eye pain	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	3	0/8 (0%)	0	0/281 (0%)	0
Eye pruritus	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	3/562 (0.5%)	3	0/8 (0%)	0	5/281 (1.8%)	5
Eye swelling	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	1/281 (0.4%)	1
Eyelid cyst	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Ocular discomfort	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Vision blurred	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	9/562 (1.6%)	11	0/8 (0%)	0	8/281 (2.8%)	8
Gastrointestinal disorders
Abdominal discomfort	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	6/281 (2.1%)	6
Abdominal distension	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	11/562 (2%)	13	0/8 (0%)	0	6/281 (2.1%)	7
Abdominal pain	0/13 (0%)	0	1/10 (10%)	1	3/11 (27.3%)	6	43/562 (7.7%)	57	0/8 (0%)	0	25/281 (8.9%)	27
Abdominal pain upper	1/13 (7.7%)	1	1/10 (10%)	1	1/11 (9.1%)	1	44/562 (7.8%)	62	1/8 (12.5%)	1	16/281 (5.7%)	19
Anal fissure	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	4/562 (0.7%)	4	0/8 (0%)	0	2/281 (0.7%)	3
Colitis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	8/562 (1.4%)	9	0/8 (0%)	0	3/281 (1.1%)	3
Constipation	3/13 (23.1%)	3	3/10 (30%)	3	6/11 (54.5%)	10	155/562 (27.6%)	211	0/8 (0%)	0	77/281 (27.4%)	97
Dental caries	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	6/562 (1.1%)	6	0/8 (0%)	0	2/281 (0.7%)	2
Diarrhoea	5/13 (38.5%)	9	2/10 (20%)	3	6/11 (54.5%)	6	155/562 (27.6%)	305	1/8 (12.5%)	2	66/281 (23.5%)	129
Dry mouth	1/13 (7.7%)	1	1/10 (10%)	1	0/11 (0%)	0	22/562 (3.9%)	23	0/8 (0%)	0	10/281 (3.6%)	14
Dyspepsia	1/13 (7.7%)	1	0/10 (0%)	0	1/11 (9.1%)	1	38/562 (6.8%)	45	0/8 (0%)	0	16/281 (5.7%)	19
Flatulence	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	11/562 (2%)	13	0/8 (0%)	0	1/281 (0.4%)	1
Gastritis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	18/562 (3.2%)	18	1/8 (12.5%)	1	7/281 (2.5%)	7
Gastrooesophageal reflux disease	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	15/562 (2.7%)	16	0/8 (0%)	0	11/281 (3.9%)	12
Gingival bleeding	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	3	1/8 (12.5%)	1	0/281 (0%)	0
Large intestinal haemorrhage	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Nausea	6/13 (46.2%)	7	2/10 (20%)	3	4/11 (36.4%)	9	251/562 (44.7%)	523	0/8 (0%)	0	130/281 (46.3%)	252
Stomatitis	0/13 (0%)	0	2/10 (20%)	2	0/11 (0%)	0	54/562 (9.6%)	76	0/8 (0%)	0	19/281 (6.8%)	22
Vomiting	3/13 (23.1%)	5	2/10 (20%)	2	6/11 (54.5%)	8	140/562 (24.9%)	245	0/8 (0%)	0	61/281 (21.7%)	105
General disorders
Asthenia	6/13 (46.2%)	16	3/10 (30%)	8	3/11 (27.3%)	6	107/562 (19%)	193	0/8 (0%)	0	47/281 (16.7%)	84
Chest pain	2/13 (15.4%)	2	1/10 (10%)	1	0/11 (0%)	0	25/562 (4.4%)	27	0/8 (0%)	0	17/281 (6%)	20
Chills	1/13 (7.7%)	1	1/10 (10%)	1	0/11 (0%)	0	16/562 (2.8%)	18	1/8 (12.5%)	1	6/281 (2.1%)	6
Fatigue	1/13 (7.7%)	1	2/10 (20%)	3	1/11 (9.1%)	1	180/562 (32%)	257	0/8 (0%)	0	96/281 (34.2%)	118
Infusion site extravasation	1/13 (7.7%)	1	0/10 (0%)	0	1/11 (9.1%)	1	3/562 (0.5%)	3	0/8 (0%)	0	0/281 (0%)	0
Infusion site pain	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Injection site reaction	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	2/562 (0.4%)	2	0/8 (0%)	0	1/281 (0.4%)	1
Malaise	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	25/562 (4.4%)	38	0/8 (0%)	0	14/281 (5%)	25
Mucosal dryness	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Mucosal inflammation	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	31/562 (5.5%)	41	0/8 (0%)	0	14/281 (5%)	21
Oedema	1/13 (7.7%)	1	0/10 (0%)	0	1/11 (9.1%)	1	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Oedema peripheral	5/13 (38.5%)	5	0/10 (0%)	0	0/11 (0%)	0	65/562 (11.6%)	84	0/8 (0%)	0	29/281 (10.3%)	42
Pyrexia	3/13 (23.1%)	3	2/10 (20%)	2	2/11 (18.2%)	4	98/562 (17.4%)	149	1/8 (12.5%)	2	55/281 (19.6%)	86
Thirst	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	2
Hepatobiliary disorders
Hepatic function abnormal	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	5/562 (0.9%)	6	1/8 (12.5%)	1	3/281 (1.1%)	3
Immune system disorders
Contrast media allergy	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	1/8 (12.5%)	1	0/281 (0%)	0
Hypersensitivity	0/13 (0%)	0	2/10 (20%)	3	0/11 (0%)	0	8/562 (1.4%)	9	0/8 (0%)	0	8/281 (2.8%)	16
Infections and infestations
Cellulitis	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	8/562 (1.4%)	8	0/8 (0%)	0	4/281 (1.4%)	5
Conjunctivitis	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1	7/562 (1.2%)	9	0/8 (0%)	0	3/281 (1.1%)	13
Conjunctivitis viral	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Cystitis	0/13 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2	11/562 (2%)	13	0/8 (0%)	0	3/281 (1.1%)	5
Erythema infectiosum	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Gastroenteritis	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	8/562 (1.4%)	9	0/8 (0%)	0	5/281 (1.8%)	6
Gastrointestinal infection	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Hordeolum	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	2/281 (0.7%)	2
Influenza	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	2	28/562 (5%)	30	0/8 (0%)	0	7/281 (2.5%)	9
Nasopharyngitis	3/13 (23.1%)	3	0/10 (0%)	0	1/11 (9.1%)	1	52/562 (9.3%)	75	1/8 (12.5%)	1	21/281 (7.5%)	27
Oral candidiasis	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1	7/562 (1.2%)	7	0/8 (0%)	0	4/281 (1.4%)	6
Oropharyngeal candidiasis	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Pharyngitis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	8/562 (1.4%)	8	0/8 (0%)	0	5/281 (1.8%)	8
Rash pustular	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	4	0/8 (0%)	0	1/281 (0.4%)	1
Rhinitis	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	5/562 (0.9%)	5	0/8 (0%)	0	6/281 (2.1%)	8
Skin infection	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	6/562 (1.1%)	7	0/8 (0%)	0	4/281 (1.4%)	4
Tonsillitis	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	8/562 (1.4%)	9	0/8 (0%)	0	1/281 (0.4%)	1
Upper respiratory tract infection	5/13 (38.5%)	5	3/10 (30%)	4	1/11 (9.1%)	8	58/562 (10.3%)	94	0/8 (0%)	0	25/281 (8.9%)	34
Urinary tract infection	1/13 (7.7%)	2	1/10 (10%)	1	1/11 (9.1%)	1	48/562 (8.5%)	68	1/8 (12.5%)	1	13/281 (4.6%)	14
Viral diarrhoea	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Viral infection	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	8/562 (1.4%)	11	0/8 (0%)	0	4/281 (1.4%)	6
Viral upper respiratory tract infection	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	5	0/8 (0%)	0	2/281 (0.7%)	2
Injury, poisoning and procedural complications
Contusion	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	9/562 (1.6%)	10	0/8 (0%)	0	3/281 (1.1%)	3
Incision site pain	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Limb injury	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Thermal burn	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	2	4/562 (0.7%)	4	0/8 (0%)	0	0/281 (0%)	0
Wound complication	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Investigations
Alanine aminotransferase increased	1/13 (7.7%)	1	1/10 (10%)	2	2/11 (18.2%)	28	139/562 (24.7%)	242	1/8 (12.5%)	1	54/281 (19.2%)	81
Amylase increased	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Aspartate aminotransferase increased	1/13 (7.7%)	1	1/10 (10%)	2	2/11 (18.2%)	17	131/562 (23.3%)	224	0/8 (0%)	0	46/281 (16.4%)	69
Blood alkaline phosphatase increased	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	50/562 (8.9%)	79	1/8 (12.5%)	1	22/281 (7.8%)	26
Blood cholesterol increased	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	3	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Blood corticotrophin increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	1/8 (12.5%)	1	0/281 (0%)	0
Blood iron decreased	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Blood lactate dehydrogenase increased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	31/562 (5.5%)	34	0/8 (0%)	0	16/281 (5.7%)	17
Blood thyroid stimulating hormone increased	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	11/562 (2%)	11	0/8 (0%)	0	3/281 (1.1%)	3
Cortisol decreased	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	1/281 (0.4%)	1
Gamma-glutamyltransferase increased	1/13 (7.7%)	1	0/10 (0%)	0	2/11 (18.2%)	2	20/562 (3.6%)	35	0/8 (0%)	0	8/281 (2.8%)	11
Haemoglobin decreased	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	3	14/562 (2.5%)	20	0/8 (0%)	0	3/281 (1.1%)	4
Lipase increased	1/13 (7.7%)	1	0/10 (0%)	0	1/11 (9.1%)	1	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Lymphocyte count decreased	0/13 (0%)	0	3/10 (30%)	7	1/11 (9.1%)	1	30/562 (5.3%)	88	2/8 (25%)	5	11/281 (3.9%)	32
Lymphocyte percentage decreased	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	36	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Neutrophil count decreased	2/13 (15.4%)	2	5/10 (50%)	17	1/11 (9.1%)	1	128/562 (22.8%)	665	2/8 (25%)	9	75/281 (26.7%)	311
Neutrophil percentage decreased	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	6/562 (1.1%)	24	0/8 (0%)	0	1/281 (0.4%)	9
Platelet count decreased	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	87/562 (15.5%)	346	1/8 (12.5%)	6	44/281 (15.7%)	125
Transaminases increased	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	4	0/8 (0%)	0	4/281 (1.4%)	4
Weight decreased	1/13 (7.7%)	2	4/10 (40%)	5	1/11 (9.1%)	1	50/562 (8.9%)	55	0/8 (0%)	0	12/281 (4.3%)	13
Weight increased	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	2	14/562 (2.5%)	14	0/8 (0%)	0	7/281 (2.5%)	8
White blood cell count decreased	0/13 (0%)	0	5/10 (50%)	20	2/11 (18.2%)	3	106/562 (18.9%)	497	2/8 (25%)	8	54/281 (19.2%)	210
Metabolism and nutrition disorders
Decreased appetite	8/13 (61.5%)	12	2/10 (20%)	2	2/11 (18.2%)	4	118/562 (21%)	140	0/8 (0%)	0	39/281 (13.9%)	49
Hyperglycaemia	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	4	27/562 (4.8%)	40	0/8 (0%)	0	11/281 (3.9%)	11
Hyperuricaemia	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	37	9/562 (1.6%)	13	0/8 (0%)	0	8/281 (2.8%)	9
Hypoalbuminaemia	0/13 (0%)	0	1/10 (10%)	1	2/11 (18.2%)	28	19/562 (3.4%)	30	0/8 (0%)	0	11/281 (3.9%)	11
Hypoglycaemia	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	3	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Hypokalaemia	0/13 (0%)	0	1/10 (10%)	4	1/11 (9.1%)	2	28/562 (5%)	47	0/8 (0%)	0	14/281 (5%)	19
Hyponatraemia	1/13 (7.7%)	1	0/10 (0%)	0	1/11 (9.1%)	1	12/562 (2.1%)	14	0/8 (0%)	0	6/281 (2.1%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	3/13 (23.1%)	3	1/10 (10%)	1	2/11 (18.2%)	2	120/562 (21.4%)	197	0/8 (0%)	0	50/281 (17.8%)	74
Arthritis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	6/562 (1.1%)	8	0/8 (0%)	0	2/281 (0.7%)	2
Back pain	2/13 (15.4%)	2	0/10 (0%)	0	0/11 (0%)	0	73/562 (13%)	90	1/8 (12.5%)	2	42/281 (14.9%)	49
Bone pain	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	22/562 (3.9%)	25	0/8 (0%)	0	17/281 (6%)	21
Coccydynia	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Groin pain	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	5/562 (0.9%)	6	0/8 (0%)	0	1/281 (0.4%)	1
Joint swelling	0/13 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2	2/562 (0.4%)	3	0/8 (0%)	0	1/281 (0.4%)	1
Musculoskeletal chest pain	1/13 (7.7%)	1	1/10 (10%)	1	0/11 (0%)	0	28/562 (5%)	31	0/8 (0%)	0	13/281 (4.6%)	16
Musculoskeletal pain	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	7/562 (1.2%)	12	0/8 (0%)	0	3/281 (1.1%)	4
Musculoskeletal stiffness	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	3/562 (0.5%)	3	0/8 (0%)	0	1/281 (0.4%)	1
Myalgia	0/13 (0%)	0	3/10 (30%)	3	2/11 (18.2%)	3	58/562 (10.3%)	82	0/8 (0%)	0	34/281 (12.1%)	57
Neck pain	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1	25/562 (4.4%)	28	0/8 (0%)	0	20/281 (7.1%)	24
Osteoporosis	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Pain in extremity	3/13 (23.1%)	3	0/10 (0%)	0	0/11 (0%)	0	56/562 (10%)	67	0/8 (0%)	0	41/281 (14.6%)	46
Pain in jaw	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	10/562 (1.8%)	11	0/8 (0%)	0	2/281 (0.7%)	2
Spinal pain	0/13 (0%)	0	0/10 (0%)	0	2/11 (18.2%)	2	5/562 (0.9%)	5	0/8 (0%)	0	2/281 (0.7%)	2
Nervous system disorders
Ataxia	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Dementia Alzheimer's type	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Dizziness	1/13 (7.7%)	1	3/10 (30%)	4	0/11 (0%)	0	52/562 (9.3%)	60	0/8 (0%)	0	24/281 (8.5%)	33
Dysgeusia	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	54/562 (9.6%)	63	0/8 (0%)	0	15/281 (5.3%)	18
Headache	2/13 (15.4%)	3	5/10 (50%)	7	1/11 (9.1%)	1	111/562 (19.8%)	184	0/8 (0%)	0	65/281 (23.1%)	102
Lethargy	1/13 (7.7%)	2	0/10 (0%)	0	1/11 (9.1%)	1	11/562 (2%)	15	0/8 (0%)	0	3/281 (1.1%)	5
Mental impairment	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Neuropathy peripheral	4/13 (30.8%)	6	2/10 (20%)	2	1/11 (9.1%)	1	62/562 (11%)	72	0/8 (0%)	0	35/281 (12.5%)	50
Neurotoxicity	2/13 (15.4%)	3	1/10 (10%)	2	0/11 (0%)	0	4/562 (0.7%)	7	0/8 (0%)	0	4/281 (1.4%)	7
Paraesthesia	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	24/562 (4.3%)	31	0/8 (0%)	0	15/281 (5.3%)	15
Peripheral motor neuropathy	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	2/562 (0.4%)	2	0/8 (0%)	0	2/281 (0.7%)	2
Peripheral sensory neuropathy	1/13 (7.7%)	1	3/10 (30%)	4	2/11 (18.2%)	2	49/562 (8.7%)	55	0/8 (0%)	0	20/281 (7.1%)	22
Polyneuropathy	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	12/562 (2.1%)	12	0/8 (0%)	0	0/281 (0%)	0
Presyncope	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	6	0/8 (0%)	0	4/281 (1.4%)	5
Somnolence	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	9/562 (1.6%)	9	0/8 (0%)	0	6/281 (2.1%)	8
Taste disorder	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	8/562 (1.4%)	9	0/8 (0%)	0	5/281 (1.8%)	5
Psychiatric disorders
Anxiety	0/13 (0%)	0	2/10 (20%)	2	3/11 (27.3%)	4	22/562 (3.9%)	22	0/8 (0%)	0	11/281 (3.9%)	11
Depressed mood	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	3/562 (0.5%)	4	0/8 (0%)	0	2/281 (0.7%)	4
Depression	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	20/562 (3.6%)	20	0/8 (0%)	0	13/281 (4.6%)	13
Insomnia	1/13 (7.7%)	2	2/10 (20%)	2	2/11 (18.2%)	2	47/562 (8.4%)	52	0/8 (0%)	0	27/281 (9.6%)	31
Persistent depressive disorder	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Stress	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Renal and urinary disorders
Dysuria	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	12/562 (2.1%)	12	0/8 (0%)	0	3/281 (1.1%)	3
Polyuria	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Reproductive system and breast disorders
Breast pain	1/13 (7.7%)	1	0/10 (0%)	0	1/11 (9.1%)	1	24/562 (4.3%)	29	0/8 (0%)	0	14/281 (5%)	14
Respiratory, thoracic and mediastinal disorders
Asthma	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	2/562 (0.4%)	2	0/8 (0%)	0	1/281 (0.4%)	1
Bronchostenosis	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Cough	2/13 (15.4%)	2	4/10 (40%)	4	2/11 (18.2%)	2	117/562 (20.8%)	153	0/8 (0%)	0	49/281 (17.4%)	58
Dyspnoea	1/13 (7.7%)	1	2/10 (20%)	3	1/11 (9.1%)	1	69/562 (12.3%)	82	0/8 (0%)	0	37/281 (13.2%)	43
Dyspnoea exertional	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	5/562 (0.9%)	5	0/8 (0%)	0	5/281 (1.8%)	6
Epistaxis	0/13 (0%)	0	2/10 (20%)	3	0/11 (0%)	0	20/562 (3.6%)	26	0/8 (0%)	0	17/281 (6%)	20
Haemoptysis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	2/281 (0.7%)	2
Nasal dryness	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	1/562 (0.2%)	1	1/8 (12.5%)	1	1/281 (0.4%)	1
Nasal pruritus	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	1/8 (12.5%)	1	0/281 (0%)	0
Oropharyngeal pain	0/13 (0%)	0	0/10 (0%)	0	0/11 (0%)	0	29/562 (5.2%)	32	0/8 (0%)	0	18/281 (6.4%)	25
Pneumothorax	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/562 (0.2%)	1	0/8 (0%)	0	3/281 (1.1%)	3
Productive cough	1/13 (7.7%)	1	1/10 (10%)	1	0/11 (0%)	0	12/562 (2.1%)	12	0/8 (0%)	0	13/281 (4.6%)	15
Pulmonary embolism	1/13 (7.7%)	2	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	4/281 (1.4%)	4
Sinus congestion	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Throat irritation	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	4/13 (30.8%)	4	5/10 (50%)	5	2/11 (18.2%)	2	190/562 (33.8%)	196	0/8 (0%)	0	97/281 (34.5%)	97
Butterfly rash	1/13 (7.7%)	2	0/10 (0%)	0	0/11 (0%)	0	0/562 (0%)	0	0/8 (0%)	0	0/281 (0%)	0
Dermatitis acneiform	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	3	11/562 (2%)	11	0/8 (0%)	0	6/281 (2.1%)	7
Dermatitis contact	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	7/562 (1.2%)	8	0/8 (0%)	0	4/281 (1.4%)	4
Drug eruption	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Dry skin	0/13 (0%)	0	1/10 (10%)	1	1/11 (9.1%)	1	16/562 (2.8%)	18	0/8 (0%)	0	10/281 (3.6%)	10
Dyshidrotic eczema	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	2/562 (0.4%)	2	0/8 (0%)	0	0/281 (0%)	0
Erythema	1/13 (7.7%)	1	1/10 (10%)	1	0/11 (0%)	0	23/562 (4.1%)	25	0/8 (0%)	0	11/281 (3.9%)	18
Erythema nodosum	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Hyperhidrosis	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	7/562 (1.2%)	7	0/8 (0%)	0	4/281 (1.4%)	4
Nail discolouration	1/13 (7.7%)	1	1/10 (10%)	1	0/11 (0%)	0	7/562 (1.2%)	7	0/8 (0%)	0	10/281 (3.6%)	10
Nail dystrophy	1/13 (7.7%)	1	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	1/281 (0.4%)	1
Onychalgia	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	3/562 (0.5%)	3	0/8 (0%)	0	3/281 (1.1%)	4
Palmar-plantar erythrodysaesthesia syndrome	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	3/562 (0.5%)	3	0/8 (0%)	0	2/281 (0.7%)	2
Pruritus	3/13 (23.1%)	3	3/10 (30%)	6	1/11 (9.1%)	1	85/562 (15.1%)	119	1/8 (12.5%)	1	32/281 (11.4%)	39
Rash	2/13 (15.4%)	2	2/10 (20%)	4	3/11 (27.3%)	4	110/562 (19.6%)	154	0/8 (0%)	0	34/281 (12.1%)	44
Rash maculo-papular	0/13 (0%)	0	3/10 (30%)	3	0/11 (0%)	0	25/562 (4.4%)	41	0/8 (0%)	0	10/281 (3.6%)	10
Rash papular	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	3/562 (0.5%)	4	0/8 (0%)	0	0/281 (0%)	0
Rash pruritic	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	6/562 (1.1%)	7	0/8 (0%)	0	2/281 (0.7%)	2
Skin hyperpigmentation	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	7/562 (1.2%)	7	0/8 (0%)	0	1/281 (0.4%)	1
Skin lesion	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	4/562 (0.7%)	5	1/8 (12.5%)	1	4/281 (1.4%)	4
Skin mass	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	1/562 (0.2%)	1	0/8 (0%)	0	0/281 (0%)	0
Urticaria	0/13 (0%)	0	1/10 (10%)	2	1/11 (9.1%)	1	11/562 (2%)	15	0/8 (0%)	0	3/281 (1.1%)	4
Vascular disorders
Flushing	0/13 (0%)	0	1/10 (10%)	1	0/11 (0%)	0	11/562 (2%)	22	0/8 (0%)	0	3/281 (1.1%)	3
Haematoma	1/13 (7.7%)	1	0/10 (0%)	0	0/11 (0%)	0	5/562 (0.9%)	6	0/8 (0%)	0	2/281 (0.7%)	2
Hot flush	1/13 (7.7%)	1	1/10 (10%)	2	0/11 (0%)	0	21/562 (3.7%)	22	0/8 (0%)	0	10/281 (3.6%)	14
Hypotension	3/13 (23.1%)	3	0/10 (0%)	0	0/11 (0%)	0	11/562 (2%)	11	0/8 (0%)	0	9/281 (3.2%)	10
Lymphoedema	0/13 (0%)	0	0/10 (0%)	0	1/11 (9.1%)	1	16/562 (2.8%)	17	0/8 (0%)	0	11/281 (3.9%)	11

Limitations/Caveats

[Not Specified]

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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.

Results Point of Contact

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

Responsible Party:

Merck Sharp & Dohme LLC

ClinicalTrials.gov Identifier:

NCT02819518

Other Study ID Numbers:

3475-355
163422
MK-3475-355
KEYNOTE-355
2016-001432-35

First Posted:

Jun 30, 2016

Last Update Posted:

Jul 25, 2022

Last Verified:

Jul 1, 2022

Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (MK-3475-355/KEYNOTE-355)

Study Details

Study Description

Brief Summary

The primary hypotheses are that:

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Additional Information:

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

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Outcome Measure Data

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Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Results Point of Contact