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)
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)
4 other identifiers
interventional
60
0 countries
N/A
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2016
Typical duration for phase_1
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 2, 2015
CompletedFirst Posted
Study publicly available on registry
December 4, 2015
CompletedStudy Start
First participant enrolled
January 27, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2018
CompletedResults Posted
Study results publicly available
October 24, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
November 18, 2019
CompletedSeptember 10, 2020
August 1, 2020
2.3 years
December 2, 2015
May 14, 2019
August 21, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
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)
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.
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.
Number of Participants Who Experienced an Adverse Event (AE)
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.
Up to approximately 28 months (through Interim database cut-off date of 31-May-2018)
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
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.
Up to approximately 28 months (through Interim database cut-off date of 31-May-2018)
Secondary Outcomes (10)
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)
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)
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.
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.
Event-Free Survival (EFS) Rate at Month 6
Month 6
- +5 more secondary outcomes
Study Arms (6)
Cohort A: KNp / KAC
EXPERIMENTALParticipants 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.
Cohort B: KNpCb (Regimen 1) / KAC
EXPERIMENTALParticipants 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.
Cohort C: KNpCb (Regimen 2) / KAC
EXPERIMENTALParticipants 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.
Cohort D: KNpCb (Regimen 3) / KAC
EXPERIMENTALParticipants 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.
Cohort E: KTCb (Regimen 1) / KAC
EXPERIMENTALParticipants 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.
Cohort F: KTCb (Regimen 2) / KAC
EXPERIMENTALParticipants 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.
Interventions
200 mg administered Q3W as an IV infusion.
125 mg/m\^2 or 100 mg/m\^2 administered weekly as an IV infusion, according to allocation.
60 mg/m\^2 administered Q3W as an IV injection.
600 mg/m\^2 administered Q3W as an IV infusion.
AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.
80 mg/m\^2 or 70 mg/m\^2 administered weekly as an IV infusion, according to allocation.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Related Publications (3)
Schmid P, Salgado R, Park YH, Munoz-Couselo E, Kim SB, Sohn J, Im SA, Foukakis T, Kuemmel S, Dent R, Yin L, Wang A, Tryfonidis K, Karantza V, Cortes J, Loi S. Pembrolizumab plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: results from the phase 1b open-label, multicohort KEYNOTE-173 study. Ann Oncol. 2020 May;31(5):569-581. doi: 10.1016/j.annonc.2020.01.072. Epub 2020 Feb 14.
PMID: 32278621RESULTDent R, Cortes J, Park YH, Munoz-Couselo E, Kim SB, Sohn J, Im SA, Holgado E, Foukakis T, Kummel S, Yearley J, Wang A, Nebozhyn M, Huang L, Cristescu R, Jelinic P, Karantza V, Schmid P. Molecular determinants of response to neoadjuvant pembrolizumab plus chemotherapy in patients with high-risk, early-stage, triple-negative breast cancer: exploratory analysis of the open-label, multicohort phase 1b KEYNOTE-173 study. Breast Cancer Res. 2025 Mar 11;27(1):35. doi: 10.1186/s13058-024-01946-y.
PMID: 40069763DERIVEDPerez-Garcia J, Soberino J, Racca F, Gion M, Stradella A, Cortes J. Atezolizumab in the treatment of metastatic triple-negative breast cancer. Expert Opin Biol Ther. 2020 Sep;20(9):981-989. doi: 10.1080/14712598.2020.1769063. Epub 2020 May 25.
PMID: 32450725DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Senior Vice President, Global Clinical Development
- Organization
- Merck Sharp & Dohme Corp.
Study Officials
- STUDY DIRECTOR
Medical Director
Merck Sharp & Dohme LLC
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 2, 2015
First Posted
December 4, 2015
Study Start
January 27, 2016
Primary Completion
May 31, 2018
Study Completion
November 18, 2019
Last Updated
September 10, 2020
Results First Posted
October 24, 2019
Record last verified: 2020-08
Data Sharing
- IPD Sharing
- Will share
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf