Safety and Efficacy Study of Pembrolizumab (MK-3475) in Combination With Chemotherapy as Neoadjuvant Treatment for Participants With Triple Negative Breast Cancer (TNBC) (MK-3475-173/KEYNOTE-173)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02622074
• Collaborator: (none)
• Enrollment: 60
• Arms: 6
• Actual Duration (Months): 45.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability and clinical activity of pembrolizumab (MK-3475) in combination with six chemotherapy regimens as neoadjuvant treatment for participants with triple negative breast cancer (TNBC).

Condition or Disease	Intervention/Treatment	Phase
Triple Negative Breast Neoplasms	Biological: Pembrolizumab; Drug: Nab-paclitaxel; Drug: Anthracycline (doxorubicin); Drug: Cyclophosphamide; Drug: Carboplatin; Drug: Paclitaxel	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Study to Evaluate Safety and Clinical Activity of Pembrolizumab (MK-3475) in Combination With Chemotherapy as Neoadjuvant Treatment for Triple Negative Breast Cancer (TNBC) - (KEYNOTE 173)
• Actual Study Start Date: Jan 27, 2016
• Actual Primary Completion Date: May 31, 2018
• Actual Study Completion Date: Nov 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: KNp / KAC Participants receive pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This will be followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments will be administered via intravenous (IV) infusion except for doxorubicin (A), which will be administered via IV injection. Each cycle is 21 days.	Biological: Pembrolizumab; 200 mg administered Q3W as an IV infusion.; Other Names: MK-3475 KEYTRUDA® ; Drug: Nab-paclitaxel; 125 mg/m^2 or 100 mg/m^2 administered weekly as an IV infusion, according to allocation.; Drug: Anthracycline (doxorubicin); 60 mg/m^2 administered Q3W as an IV injection.; Drug: Cyclophosphamide; 600 mg/m^2 administered Q3W as an IV infusion.
Experimental: Cohort B: KNpCb (Regimen 1) / KAC Participants first receive KNpCb Regimen 1 which consists of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This will be followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments will be administered via IV infusion except for doxorubicin (A), which will be administered via IV injection. Each cycle is 21 days.	Biological: Pembrolizumab; 200 mg administered Q3W as an IV infusion.; Other Names: MK-3475 KEYTRUDA® ; Drug: Nab-paclitaxel; 125 mg/m^2 or 100 mg/m^2 administered weekly as an IV infusion, according to allocation.; Drug: Anthracycline (doxorubicin); 60 mg/m^2 administered Q3W as an IV injection.; Drug: Cyclophosphamide; 600 mg/m^2 administered Q3W as an IV infusion.; Drug: Carboplatin; AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.
Experimental: Cohort C: KNpCb (Regimen 2) / KAC Participants first receive KNpCb Regimen 2 which consists of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This will be followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments will be administered via IV infusion except for doxorubicin (A), which will be administered via IV injection. Each cycle is 21 days.	Biological: Pembrolizumab; 200 mg administered Q3W as an IV infusion.; Other Names: MK-3475 KEYTRUDA® ; Drug: Nab-paclitaxel; 125 mg/m^2 or 100 mg/m^2 administered weekly as an IV infusion, according to allocation.; Drug: Anthracycline (doxorubicin); 60 mg/m^2 administered Q3W as an IV injection.; Drug: Cyclophosphamide; 600 mg/m^2 administered Q3W as an IV infusion.; Drug: Carboplatin; AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.
Experimental: Cohort D: KNpCb (Regimen 3) / KAC Participants first receive KNpCb Regimen 3 which consists of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This will be followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments will be administered via IV infusion except for doxorubicin (A), which will be administered via IV injection. Each cycle is 21 days.	Biological: Pembrolizumab; 200 mg administered Q3W as an IV infusion.; Other Names: MK-3475 KEYTRUDA® ; Drug: Nab-paclitaxel; 125 mg/m^2 or 100 mg/m^2 administered weekly as an IV infusion, according to allocation.; Drug: Anthracycline (doxorubicin); 60 mg/m^2 administered Q3W as an IV injection.; Drug: Cyclophosphamide; 600 mg/m^2 administered Q3W as an IV infusion.; Drug: Carboplatin; AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.
Experimental: Cohort E: KTCb (Regimen 1) / KAC Participants first receive KTCb Regimen 1 which consists of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This will be followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments will be administered via IV infusion except for doxorubicin (A), which will be administered via IV injection. Each cycle is 21 days.	Biological: Pembrolizumab; 200 mg administered Q3W as an IV infusion.; Other Names: MK-3475 KEYTRUDA® ; Drug: Anthracycline (doxorubicin); 60 mg/m^2 administered Q3W as an IV injection.; Drug: Cyclophosphamide; 600 mg/m^2 administered Q3W as an IV infusion.; Drug: Carboplatin; AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.; Drug: Paclitaxel; 80 mg/m^2 or 70 mg/m^2 administered weekly as an IV infusion, according to allocation.
Experimental: Cohort F: KTCb (Regimen 2) / KAC Participants first receive KTCb Regimen 2 which consists of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This will be followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments will be administered via IV infusion except for doxorubicin (A), which will be administered via IV injection. Each cycle is 21 days.	Biological: Pembrolizumab; 200 mg administered Q3W as an IV infusion.; Other Names: MK-3475 KEYTRUDA® ; Drug: Anthracycline (doxorubicin); 60 mg/m^2 administered Q3W as an IV injection.; Drug: Cyclophosphamide; 600 mg/m^2 administered Q3W as an IV infusion.; Drug: Carboplatin; AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.; Drug: Paclitaxel; 80 mg/m^2 or 70 mg/m^2 administered weekly as an IV infusion, according to allocation.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Dose Limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0) [Cycle 1 Day 1 through end of Cycle 3 and Cycle 6 Day 1 through end of Cycle 7 (Up to ~150 days from first dose of first combination regimen); Each cycle was 21 days.]

   The following events, if considered to be study-treatment-related by the Investigator, were considered a DLT: Hematologic: Grade 4 neutropenia lasting ≥8 days; Febrile neutropenia Grade 3 or Grade 4; or Grade 4 thrombocytopenia requiring platelet transfusion, or Grade 3 thrombocytopenia with bleeding Non-hematologic: Grade 4 toxicity; Grade ≥3 symptomatic hepatic toxicities lasting >48 hours, or Grade ≥3 asymptomatic hepatic toxicities lasting ≥7 days; or Grade ≥3 non-hematologic, non-hepatic organ toxicity, with exceptions Other: Any treatment delays for ≥14 days due to unresolved toxicity; Grade 5 treatment-related adverse event (AE); A dose reduction of study treatment during the DLT evaluation period.

2. Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 28 months (through Interim database cut-off date of 31-May-2018)]

   An AE was defined as any untoward medical occurrence in a participant administered study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE either prior to or after definitive surgery is presented.

3. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [Up to approximately 28 months (through Interim database cut-off date of 31-May-2018)]

   An AE was defined as any untoward medical occurrence in a participant administered study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.

Secondary Outcome Measures

1. Pathological Complete Response (pCR) Rate Using the Definition of ypT0 ypN0 (No Invasive or Noninvasive Residual in Breast or Nodes) [Up to approximately 9 months (at the time of definitive surgery)]

   pCR rate (ypT0 ypN0; no invasive or noninvasive residual in breast or nodes) was defined as the rate of absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by American Joint Committee on Cancer (AJCC) staging criteria assessed by local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the definition of ypT0 ypN0 is presented.

2. Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 (No Invasive Residual in Breast or Nodes; Noninvasive Breast Residuals Allowed) [Up to approximately 9 months (at the time of definitive surgery)]

   pCR rate (ypT0/Tis ypN0; no invasive residual in breast or nodes; noninvasive breast residuals allowed) was defined as the rate of absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria assessed by local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the alternative definition of ypT0/Tis ypN0 is presented.

3. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Review: First Combination Regimen [At the end of Cycle 5 following treatment with the first combination regimen (KNp, KNpCb, or KTCb) (Up to ~4 months); Each cycle was 21 days.]

   ORR was defined as the percentage of participants who achieved a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions) according to RECIST 1.1 by Investigator review. Because imaging was assessed prior to surgery, a confirmation assessment of CR or PR was not obtained. Participants with missing outcome for objective response were considered non-responders. The percentage of participants who experienced a CR or PR based on RECIST 1.1 following the first combination regimen is presented.

4. Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Review: Second Combination Regimen [After completion of the second combination regimen (KAC; Cycle 9) but prior to surgery (Up to ~9 months); Each cycle was 21 days.]

   ORR was defined as the percentage of participants who achieved a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions) according to RECIST 1.1 by Investigator review. Because imaging was assessed prior to surgery, a confirmation assessment of CR or PR was not obtained. Participants with missing outcome for objective response were considered non-responders. The percentage of participants who experienced a CR or PR based on RECIST 1.1 following the second combination regimen is presented.

5. Event-Free Survival (EFS) Rate at Month 6 [Month 6]

   EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 6 are presented (through Final Analysis cut-off of 18-Nov-2019).

6. Event-Free Survival (EFS) Rate at Month 12 [Month 12]

   EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 12 are presented (through Final Analysis cut-off of 18-Nov-2019).

7. Event-Free Survival (EFS) Rate at Month 24 [Month 24]

   EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 24 are presented (through Final Analysis cut-off of 18-Nov-2019).

8. Overall Survival (OS) Rate at Month 6 [Month 6]

   OS was defined as the time from the first dose date of study treatment 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. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 6 are presented (through Final Analysis cut-off of 18-Nov-2019).

9. Overall Survival (OS) Rate at Month 12 [Month 12]

   OS was defined as the time from the first dose date of study treatment 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. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 12 are presented (through Final Analysis cut-off of 18-Nov-2019).

10. Overall Survival (OS) Rate at Month 24 [Month 24]

    OS was defined as the time from the first dose date of study treatment 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. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 24 are presented (through Final Analysis cut-off of 18-Nov-2019).

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Has previously untreated, locally advanced TNBC.

• Is able to provide 2 core needle biopsies from the primary tumor at screening to the central laboratory and agrees to have a core needle biopsy after single dose pembrolizumab treatment if tumor biopsy is feasible as judged by the investigator.

• Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

• Has adequate organ function.

• Females of childbearing potential must be willing to use adequate contraception for the course of the study through 12 months after the last dose of study drug for participants receiving cyclophosphamide and through 6 months after the last dose of study drug for participants who do not receive cyclophosphamide.

Exclusion Criteria:

• Has evidence of metastatic breast cancer, concurrent bilateral invasive breast cancer, or inflammatory breast cancer.

• Has another malignancy within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative surgery, or in situ cervical cancer.

• Has received prior chemotherapy, targeted therapy, radiation therapy, immunotherapy that targets immune checkpoints, co-stimulatory or co-inhibitory pathways for T cell receptors within the past 12 months.

• Is currently participating and receiving study therapy, or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study drug.

• Has received a live vaccine within 30 days of the first dose of study drug.

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

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.

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

• Has known active Hepatitis B or Hepatitis C.

• Has evidence of current pneumonitis.

• Has a history of non-infectious pneumonitis requiring treatment with steroids or a history of interstitial lung disease.

• Has an active infection requiring systemic therapy.

• Has significant cardiovascular disease, such as: History of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the last 6 months; Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA class III or IV

• Has 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 children within the projected duration of the study, starting with the screening visit through 12 months after the last dose of trial treatment for participants who have received cyclophosphamide, and for six months after the last dose of study medication for participants who have not.

• Has a known hypersensitivity to the components of the study drug or its analogs.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

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

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 19, 2018

More Information

Additional Information:

• Merck Oncology Clinical Trial Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02622074
• Other Study ID Numbers: 3475-173; 2015-002405-11; MK-3475-173; KEYNOTE-173
• First Posted: Dec 4, 2015
• Last Update Posted: Sep 10, 2020
• Last Verified: Aug 1, 2020

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

Study Results

Participant Flow

Pre-assignment Detail	Sixty participants were allocated and treated on study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Period Title: Overall Study
STARTED	10	10	10	10	10	10
COMPLETED	6	9	10	9	9	10
NOT COMPLETED	4	1	0	1	1	0

Baseline Characteristics

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC	Total
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Total of all reporting groups
Overall Participants	10	10	10	10	10	10	60
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.5 (11.1)	49.5 (11.3)	43.2 (6.4)	42.3 (11.2)	56.7 (11.9)	52.1 (11.3)	49.2 (11.4)
Sex: Female, Male (Count of Participants)
Female	10 100%	10 100%	10 100%	10 100%	10 100%	10 100%	60 100%
Male	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	2 20%	1 10%	0 0%	0 0%	0 0%	3 5%
Not Hispanic or Latino	10 100%	8 80%	9 90%	10 100%	10 100%	10 100%	57 95%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	5 50%	2 20%	5 50%	7 70%	1 10%	1 10%	21 35%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
White	5 50%	8 80%	5 50%	3 30%	9 90%	9 90%	39 65%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs) Graded Using National Cancer Institute Common Toxicity Criteria for Adverse Events Version 4.0 (NCI CTCAE v4.0)
Description	The following events, if considered to be study-treatment-related by the Investigator, were considered a DLT: Hematologic: Grade 4 neutropenia lasting ≥8 days; Febrile neutropenia Grade 3 or Grade 4; or Grade 4 thrombocytopenia requiring platelet transfusion, or Grade 3 thrombocytopenia with bleeding Non-hematologic: Grade 4 toxicity; Grade ≥3 symptomatic hepatic toxicities lasting >48 hours, or Grade ≥3 asymptomatic hepatic toxicities lasting ≥7 days; or Grade ≥3 non-hematologic, non-hepatic organ toxicity, with exceptions Other: Any treatment delays for ≥14 days due to unresolved toxicity; Grade 5 treatment-related adverse event (AE); A dose reduction of study treatment during the DLT evaluation period.
Time Frame	Cycle 1 Day 1 through end of Cycle 3 and Cycle 6 Day 1 through end of Cycle 7 (Up to ~150 days from first dose of first combination regimen); Each cycle was 21 days.

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Count of Participants [Participants]	2 20%	4 40%	6 60%	6 60%	0 0%	4 40%

2. Primary Outcome

Title	Number of Participants Who Experienced an Adverse Event (AE)
Description	An AE was defined as any untoward medical occurrence in a participant administered study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE either prior to or after definitive surgery is presented.
Time Frame	Up to approximately 28 months (through Interim database cut-off date of 31-May-2018)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Count of Participants [Participants]	10 100%	10 100%	10 100%	10 100%	10 100%	10 100%

3. Primary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Description	An AE was defined as any untoward medical occurrence in a participant administered study treatment and which does not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued study treatment due to an AE is presented.
Time Frame	Up to approximately 28 months (through Interim database cut-off date of 31-May-2018)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Count of Participants [Participants]	1 10%	2 20%	1 10%	5 50%	2 20%	5 50%

4. Secondary Outcome

Title	Pathological Complete Response (pCR) Rate Using the Definition of ypT0 ypN0 (No Invasive or Noninvasive Residual in Breast or Nodes)
Description	pCR rate (ypT0 ypN0; no invasive or noninvasive residual in breast or nodes) was defined as the rate of absence of residual invasive and in situ cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by American Joint Committee on Cancer (AJCC) staging criteria assessed by local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the definition of ypT0 ypN0 is presented.
Time Frame	Up to approximately 9 months (at the time of definitive surgery)

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	50.0 500%	80.0 800%	80.0 800%	60.0 600%	20.0 200%	50.0 500%

5. Secondary Outcome

Title	Pathological Complete Response (pCR) Rate Using the Definition of ypT0/Tis ypN0 (No Invasive Residual in Breast or Nodes; Noninvasive Breast Residuals Allowed)
Description	pCR rate (ypT0/Tis ypN0; no invasive residual in breast or nodes; noninvasive breast residuals allowed) was defined as the rate of absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria assessed by local pathologist at the time of definitive surgery. The percentage of participants with a pCR using the alternative definition of ypT0/Tis ypN0 is presented.
Time Frame	Up to approximately 9 months (at the time of definitive surgery)

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	60.0 600%	80.0 800%	80.0 800%	60.0 600%	30.0 300%	50.0 500%

6. Secondary Outcome

Title	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Review: First Combination Regimen
Description	ORR was defined as the percentage of participants who achieved a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions) according to RECIST 1.1 by Investigator review. Because imaging was assessed prior to surgery, a confirmation assessment of CR or PR was not obtained. Participants with missing outcome for objective response were considered non-responders. The percentage of participants who experienced a CR or PR based on RECIST 1.1 following the first combination regimen is presented.
Time Frame	At the end of Cycle 5 following treatment with the first combination regimen (KNp, KNpCb, or KTCb) (Up to ~4 months); Each cycle was 21 days.

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	60.0 600%	90.0 900%	90.0 900%	90.0 900%	60.0 600%	80.0 800%

7. Secondary Outcome

Title	Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Investigator Review: Second Combination Regimen
Description	ORR was defined as the percentage of participants who achieved a complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters [SOD] of target lesions) according to RECIST 1.1 by Investigator review. Because imaging was assessed prior to surgery, a confirmation assessment of CR or PR was not obtained. Participants with missing outcome for objective response were considered non-responders. The percentage of participants who experienced a CR or PR based on RECIST 1.1 following the second combination regimen is presented.
Time Frame	After completion of the second combination regimen (KAC; Cycle 9) but prior to surgery (Up to ~9 months); Each cycle was 21 days.

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	80.0 800%	100 1000%	100 1000%	90.0 900%	70.0 700%	90.0 900%

8. Secondary Outcome

Title	Event-Free Survival (EFS) Rate at Month 6
Description	EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 6 are presented (through Final Analysis cut-off of 18-Nov-2019).
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	90.0 900%	100.0 1000%	100.00 1000%	90.0 900%	100.0 1000%	100.0 1000%

9. Secondary Outcome

Title	Event-Free Survival (EFS) Rate at Month 12
Description	EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 12 are presented (through Final Analysis cut-off of 18-Nov-2019).
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	80.0 800%	100.0 1000%	100.0 1000%	90.0 900%	100.0 1000%	100.0 1000%

10. Secondary Outcome

Title	Event-Free Survival (EFS) Rate at Month 24
Description	EFS was defined as the time from the first dose date of study treatment to any of the following events: progression of disease that precludes definitive surgery, disease recurrence (for participants with complete surgical resection), progression (for participants with incomplete surgical resection), or death due to any cause. Participants without documented events were censored at the date of the last disease status assessment. The Kaplan-Meier estimates of the percentage of participants who were event free at Month 24 are presented (through Final Analysis cut-off of 18-Nov-2019).
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	60.0 600%	100.0 1000%	100.0 1000%	90.0 900%	90.0 900%	100.0 1000%

11. Secondary Outcome

Title	Overall Survival (OS) Rate at Month 6
Description	OS was defined as the time from the first dose date of study treatment 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. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 6 are presented (through Final Analysis cut-off of 18-Nov-2019).
Time Frame	Month 6

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	100.0 1000%	100.0 1000%	100.0 1000%	90.0 900%	100.0 1000%	100.0 1000%

12. Secondary Outcome

Title	Overall Survival (OS) Rate at Month 12
Description	OS was defined as the time from the first dose date of study treatment 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. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 12 are presented (through Final Analysis cut-off of 18-Nov-2019).
Time Frame	Month 12

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	80.0 800%	100.0 1000%	100.0 1000%	90.0 900%	100.0 1000%	100.0 1000%

13. Secondary Outcome

Title	Overall Survival (OS) Rate at Month 24
Description	OS was defined as the time from the first dose date of study treatment 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. The Kaplan-Meier estimates of the percentage of participants who were surviving at Month 24 are presented (through Final Analysis cut-off of 18-Nov-2019).
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description

The efficacy population consisted of all participants with Baseline evaluable disease by Investigator assessment who started with the recommended Phase 2 dose, regardless of dose modification during the course of the study.

Arm/Group Title	Cohort A: KNp / KAC	Cohort B: KNpCb (Regimen 1) / KAC	Cohort C: KNpCb (Regimen 2) / KAC	Cohort D: KNpCb (Regimen 3) / KAC	Cohort E: KTCb (Regimen 1) / KAC	Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at Area Under the Curve (AUC) 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.	Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
Measure Participants	10	10	10	10	10	10
Number (90% Confidence Interval) [Percentage of Participants]	70.0 700%	100.0 1000%	100.0 1000%	90.0 900%	90.0 900%	100.0 1000%

Adverse Events

Time Frame	Up to approximately 45 months (through Final Analysis cut-off date of 18-Nov-2019)
Adverse Event Reporting Description	All-Cause Mortality table includes all randomized participants. Serious and Other AEs include all randomized participants who received ≥1 dose of study drug. Per protocol, disease progression of cancer on study was not considered an AE unless considered related to study drug. Thus, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug were excluded as AEs.
Arm/Group Title	Cohort A: KNp / KAC		Cohort B: KNpCb (Regimen 1) / KAC		Cohort C: KNpCb (Regimen 2) / KAC		Cohort D: KNpCb (Regimen 3) / KAC		Cohort E: KTCb (Regimen 1) / KAC		Cohort F: KTCb (Regimen 2) / KAC
Arm/Group Description	Participants received pembrolizumab (K) 200 mg on Cycle 1 Day 1 followed by pembrolizumab 200 mg in Cycles 2-5 on Day 1 (once every 3 weeks; Q3W) PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (once each week; QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via intravenous (IV) infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.		Participants first received KNpCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 100 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 6 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.		Participants first received KNpCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.		Participants first received KNpCb Regimen 3 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS nab-paclitaxel (KNp) starting at 125 mg/m^2 in Cycles 2-5 on Days 1, 8 and 15 (QW) PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.		Participants first received KTCb Regimen 1 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 (QW) PLUS carboplatin (Cb) starting at AUC 5 in Cycles 2-5 on Day 1 (Q3W). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.		Participants first received KTCb Regimen 2 which consisted of: pembrolizumab (K) 200 mg on Cycle 1 Day 1 PLUS paclitaxel (T) starting at 80mg/m^2 in Cycles 2-5 on Days 1, 8, and 15 PLUS carboplatin (Cb) starting at AUC 2 in Cycles 2-5 on Days 1, 8 and 15 (QW). This was followed by pembrolizumab (K) 200 mg in Cycles 6-9 on Day 1 (Q3W) PLUS doxorubicin (A) 60 mg/m^2 in Cycles 6-9 on Day 1 (Q3W) PLUS cyclophosphamide (C) 600 mg/m^2 in Cycles 6-9 on Day 1 (Q3W). All treatments were administered via IV infusion except for doxorubicin (A), which was administered via IV injection. Each cycle was 21 days.
All Cause Mortality
	Cohort A: KNp / KAC		Cohort B: KNpCb (Regimen 1) / KAC		Cohort C: KNpCb (Regimen 2) / KAC		Cohort D: KNpCb (Regimen 3) / KAC		Cohort E: KTCb (Regimen 1) / KAC		Cohort F: KTCb (Regimen 2) / KAC
	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	4/10 (40%)		0/10 (0%)		0/10 (0%)		1/10 (10%)		1/10 (10%)		0/10 (0%)
Serious Adverse Events
	Cohort A: KNp / KAC		Cohort B: KNpCb (Regimen 1) / KAC		Cohort C: KNpCb (Regimen 2) / KAC		Cohort D: KNpCb (Regimen 3) / KAC		Cohort E: KTCb (Regimen 1) / KAC		Cohort F: KTCb (Regimen 2) / KAC
	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	5/10 (50%)		4/10 (40%)		8/10 (80%)		7/10 (70%)		3/10 (30%)		4/10 (40%)
Blood and lymphatic system disorders
Anaemia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Febrile neutropenia	1/10 (10%)	1	2/10 (20%)	3	4/10 (40%)	4	4/10 (40%)	6	0/10 (0%)	0	0/10 (0%)	0
Lymphadenitis	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Neutropenia	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Gastrointestinal disorders
Abdominal pain upper	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Colitis	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Diarrhoea	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Nausea	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Oesophagitis	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
General disorders
Pyrexia	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1
Hepatobiliary disorders
Autoimmune hepatitis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Infections and infestations
Influenza	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Neutropenic sepsis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Pneumocystis jirovecii pneumonia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Pneumonia	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1
Respiratory tract infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Septic shock	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Tooth infection	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Urinary tract infection	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Injury, poisoning and procedural complications
Tendon rupture	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Investigations
Alanine aminotransferase increased	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Aspartate aminotransferase increased	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Blood creatinine increased	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
White blood cell count decreased	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Nervous system disorders
Autonomic neuropathy	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Brachial plexopathy	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Ischaemic stroke	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Skin and subcutaneous tissue disorders
Subacute cutaneous lupus erythematosus	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Vascular disorders
Deep vein thrombosis	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Orthostatic hypotension	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Other (Not Including Serious) Adverse Events
	Cohort A: KNp / KAC		Cohort B: KNpCb (Regimen 1) / KAC		Cohort C: KNpCb (Regimen 2) / KAC		Cohort D: KNpCb (Regimen 3) / KAC		Cohort E: KTCb (Regimen 1) / KAC		Cohort F: KTCb (Regimen 2) / KAC
	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	10/10 (100%)		10/10 (100%)		10/10 (100%)		10/10 (100%)		10/10 (100%)		10/10 (100%)
Blood and lymphatic system disorders
Anaemia	2/10 (20%)	2	9/10 (90%)	14	7/10 (70%)	14	6/10 (60%)	7	7/10 (70%)	10	6/10 (60%)	13
Febrile neutropenia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1
Leukocytosis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Leukopenia	0/10 (0%)	0	1/10 (10%)	6	2/10 (20%)	2	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	2
Neutropenia	4/10 (40%)	10	8/10 (80%)	24	7/10 (70%)	30	8/10 (80%)	25	4/10 (40%)	5	6/10 (60%)	7
Neutrophilia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Thrombocytopenia	0/10 (0%)	0	7/10 (70%)	14	2/10 (20%)	4	4/10 (40%)	7	1/10 (10%)	1	2/10 (20%)	2
Cardiac disorders
Cardiovascular disorder	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Palpitations	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Pericardial effusion	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Sinus tachycardia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Tachycardia	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Ear and labyrinth disorders
Hypoacusis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Tinnitus	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Vertigo	2/10 (20%)	3	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Endocrine disorders
Autoimmune thyroiditis	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Hyperthyroidism	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Hypothyroidism	2/10 (20%)	2	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Thyroiditis	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Eye disorders
Blepharospasm	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Dry eye	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Eye disorder	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Lacrimation increased	2/10 (20%)	2	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Visual acuity reduced	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Visual impairment	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/10 (0%)	0	3/10 (30%)	3	3/10 (30%)	4	1/10 (10%)	2	1/10 (10%)	1	2/10 (20%)	2
Abdominal pain lower	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	3	0/10 (0%)	0	0/10 (0%)	0
Abdominal pain upper	1/10 (10%)	5	2/10 (20%)	3	2/10 (20%)	4	1/10 (10%)	2	1/10 (10%)	1	0/10 (0%)	0
Anal fissure	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Anal inflammation	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	2	0/10 (0%)	0	0/10 (0%)	0
Constipation	2/10 (20%)	2	3/10 (30%)	4	4/10 (40%)	7	1/10 (10%)	1	5/10 (50%)	7	4/10 (40%)	7
Diarrhoea	0/10 (0%)	0	0/10 (0%)	0	4/10 (40%)	9	4/10 (40%)	7	5/10 (50%)	7	3/10 (30%)	6
Dyspepsia	4/10 (40%)	6	3/10 (30%)	6	1/10 (10%)	1	2/10 (20%)	3	4/10 (40%)	5	2/10 (20%)	2
Dysphagia	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Enterocolitis	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Epigastric discomfort	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Gastritis	2/10 (20%)	2	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Haemorrhoids	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	1/10 (10%)	1
Hypoaesthesia oral	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Lip oedema	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Melaena	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Mouth ulceration	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Nausea	6/10 (60%)	17	8/10 (80%)	22	10/10 (100%)	23	5/10 (50%)	13	8/10 (80%)	22	6/10 (60%)	9
Oesophageal pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Oral mucosal blistering	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Oral pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Paraesthesia oral	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Proctalgia	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Rectal haemorrhage	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Rectal tenesmus	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Stomatitis	3/10 (30%)	3	2/10 (20%)	3	2/10 (20%)	5	4/10 (40%)	4	1/10 (10%)	1	0/10 (0%)	0
Toothache	0/10 (0%)	0	1/10 (10%)	1	2/10 (20%)	2	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Vomiting	4/10 (40%)	9	2/10 (20%)	3	4/10 (40%)	5	5/10 (50%)	11	4/10 (40%)	9	2/10 (20%)	4
General disorders
Asthenia	3/10 (30%)	9	6/10 (60%)	8	3/10 (30%)	8	1/10 (10%)	1	2/10 (20%)	5	2/10 (20%)	3
Chest discomfort	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	2	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Chest pain	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Chills	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	2/10 (20%)	2
Facial pain	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Fatigue	5/10 (50%)	7	3/10 (30%)	5	5/10 (50%)	12	3/10 (30%)	6	6/10 (60%)	6	6/10 (60%)	9
Influenza like illness	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Injection site induration	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Injection site pain	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Malaise	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Mucosal dryness	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Mucosal inflammation	2/10 (20%)	2	2/10 (20%)	2	4/10 (40%)	4	0/10 (0%)	0	2/10 (20%)	2	6/10 (60%)	8
Oedema	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Oedema peripheral	2/10 (20%)	2	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Pain	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	2/10 (20%)	2	0/10 (0%)	0
Peripheral swelling	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Puncture site swelling	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Pyrexia	3/10 (30%)	3	2/10 (20%)	2	2/10 (20%)	2	4/10 (40%)	4	2/10 (20%)	2	2/10 (20%)	2
Sensation of foreign body	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Temperature regulation disorder	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Physical deconditioning	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Immune system disorders
Food allergy	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Hypersensitivity	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Infections and infestations
Aspergillus infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Candida infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1
Cellulitis	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Conjunctivitis	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Cytomegalovirus infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
External ear cellulitis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Herpes simplex	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Hordeolum	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Klebsiella infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Lower respiratory tract infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Nasopharyngitis	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Neutropenic infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Oral candidiasis	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0
Oral fungal infection	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Pulpitis dental	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Rhinitis	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Staphylococcal infection	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Upper respiratory tract infection	1/10 (10%)	2	0/10 (0%)	0	3/10 (30%)	4	3/10 (30%)	3	1/10 (10%)	1	0/10 (0%)	0
Urinary tract infection	2/10 (20%)	2	2/10 (20%)	2	0/10 (0%)	0	2/10 (20%)	3	2/10 (20%)	4	0/10 (0%)	0
Vulvovaginal candidiasis	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Vulvovaginitis	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Wound infection	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Injury, poisoning and procedural complications
Allergic transfusion reaction	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Infusion related reaction	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Procedural pain	3/10 (30%)	3	1/10 (10%)	1	2/10 (20%)	2	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Sunburn	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Investigations
Alanine aminotransferase increased	3/10 (30%)	4	1/10 (10%)	2	3/10 (30%)	3	2/10 (20%)	3	0/10 (0%)	0	4/10 (40%)	4
Aspartate aminotransferase increased	2/10 (20%)	2	1/10 (10%)	2	2/10 (20%)	2	1/10 (10%)	2	0/10 (0%)	0	3/10 (30%)	3
Blood creatinine increased	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Blood lactate dehydrogenase increased	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	2	0/10 (0%)	0	0/10 (0%)	0
Blood phosphorus decreased	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Blood potassium decreased	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	2
Hepatic enzyme decreased	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Neutrophil count decreased	2/10 (20%)	3	2/10 (20%)	5	3/10 (30%)	5	2/10 (20%)	4	5/10 (50%)	11	2/10 (20%)	4
Platelet count decreased	0/10 (0%)	0	2/10 (20%)	2	2/10 (20%)	3	1/10 (10%)	1	2/10 (20%)	3	1/10 (10%)	1
Respirovirus test positive	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Vitamin D increased	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Weight decreased	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
White blood cell count	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
White blood cell count decreased	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	4	1/10 (10%)	1	2/10 (20%)	3	1/10 (10%)	2
Metabolism and nutrition disorders
Decreased appetite	1/10 (10%)	1	2/10 (20%)	2	5/10 (50%)	6	4/10 (40%)	8	5/10 (50%)	7	4/10 (40%)	4
Hypercalcaemia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Hyperkalaemia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Hypoalbuminaemia	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Hypocalcaemia	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Hypokalaemia	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	3	0/10 (0%)	0
Hypomagnesaemia	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Hyponatraemia	2/10 (20%)	2	0/10 (0%)	0	0/10 (0%)	0	2/10 (20%)	2	0/10 (0%)	0	0/10 (0%)	0
Hypophosphataemia	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Vitamin B12 deficiency	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/10 (10%)	1	2/10 (20%)	2	2/10 (20%)	2	1/10 (10%)	2	3/10 (30%)	8	2/10 (20%)	4
Back pain	0/10 (0%)	0	3/10 (30%)	3	3/10 (30%)	3	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Bone pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0
Joint noise	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Muscle spasms	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Muscular weakness	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Myalgia	2/10 (20%)	3	1/10 (10%)	1	4/10 (40%)	7	3/10 (30%)	6	0/10 (0%)	0	1/10 (10%)	1
Spondylitis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Tendonitis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Muscle discomfort	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oligodendroglioma	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Nervous system disorders
Ageusia	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	2	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Disturbance in attention	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Dizziness	1/10 (10%)	1	0/10 (0%)	0	3/10 (30%)	4	0/10 (0%)	0	2/10 (20%)	2	0/10 (0%)	0
Dysgeusia	2/10 (20%)	2	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Facial nerve disorder	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Headache	4/10 (40%)	4	3/10 (30%)	4	5/10 (50%)	8	0/10 (0%)	0	2/10 (20%)	2	1/10 (10%)	1
Hypoaesthesia	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Lethargy	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	3	0/10 (0%)	0
Neuropathy peripheral	2/10 (20%)	2	0/10 (0%)	0	3/10 (30%)	3	2/10 (20%)	2	3/10 (30%)	3	3/10 (30%)	3
Neurotoxicity	0/10 (0%)	0	2/10 (20%)	2	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0
Paraesthesia	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	2	1/10 (10%)	1	1/10 (10%)	1	1/10 (10%)	1
Parosmia	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Peripheral sensory neuropathy	5/10 (50%)	5	1/10 (10%)	1	4/10 (40%)	6	2/10 (20%)	3	0/10 (0%)	0	2/10 (20%)	2
Petit mal epilepsy	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Polyneuropathy	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Syncope	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	2/10 (20%)	2	0/10 (0%)	0
Taste disorder	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Psychiatric disorders
Anxiety	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Confusional state	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Depressed mood	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Depression	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Insomnia	2/10 (20%)	2	2/10 (20%)	2	3/10 (30%)	3	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Libido increased	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Personality change	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Renal and urinary disorders
Calculus urinary	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Renal pain	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Reproductive system and breast disorders
Breast pain	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Menstrual disorder	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Pruritus genital	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Vaginal discharge	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Vulval ulceration	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Vulvovaginal discomfort	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Vulvovaginal dryness	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Cough	3/10 (30%)	3	2/10 (20%)	2	1/10 (10%)	1	2/10 (20%)	3	1/10 (10%)	2	2/10 (20%)	2
Dyspnoea	0/10 (0%)	0	1/10 (10%)	1	2/10 (20%)	2	2/10 (20%)	2	1/10 (10%)	1	2/10 (20%)	2
Dyspnoea exertional	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Epistaxis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Nasal congestion	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Nasal dryness	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Oropharyngeal pain	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	1/10 (10%)	1	1/10 (10%)	1
Pharyngeal inflammation	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Productive cough	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Rhinorrhoea	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1
Alopecia	7/10 (70%)	7	4/10 (40%)	4	5/10 (50%)	5	5/10 (50%)	5	5/10 (50%)	5	4/10 (40%)	4
Dermatitis acneiform	0/10 (0%)	0	0/10 (0%)	0	2/10 (20%)	2	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0
Dry skin	1/10 (10%)	1	2/10 (20%)	2	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Eczema	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1
Nail discolouration	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Nail disorder	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Nail dystrophy	1/10 (10%)	2	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Night sweats	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Onychalgia	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Onycholysis	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Pruritus	3/10 (30%)	3	1/10 (10%)	1	3/10 (30%)	3	2/10 (20%)	3	1/10 (10%)	1	1/10 (10%)	1
Rash	5/10 (50%)	6	1/10 (10%)	2	4/10 (40%)	6	5/10 (50%)	5	4/10 (40%)	5	2/10 (20%)	3
Rash erythematous	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0
Rash maculo-papular	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	3/10 (30%)	3	0/10 (0%)	0	0/10 (0%)	0
Rash papular	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Rash pruritic	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	2/10 (20%)	2	0/10 (0%)	0
Skin hyperpigmentation	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	2/10 (20%)	2	0/10 (0%)	0	0/10 (0%)	0
Skin hypopigmentation	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0
Vascular disorders
Embolism	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Embolism venous	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0
Flushing	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Hot flush	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0	1/10 (10%)	1	1/10 (10%)	1	0/10 (0%)	0
Hypotension	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Thrombophlebitis	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0
Vein disorder	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	0/10 (0%)	0	1/10 (10%)	1	0/10 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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