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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)

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Merck Sharp & Dohme Corp.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT02622074
First received: December 2, 2015
Last updated: August 18, 2017
Last verified: August 2017
  Purpose

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).

The primary objectives of this study are: 1) to determine the safety and tolerability and 2) to establish a recommended Phase 2 dose for the six combination regimens as a neoadjuvant treatments for participants with TNBC.


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

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Merck Sharp & Dohme Corp.:

Primary Outcome Measures:
  • Number of Participants with Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 90 days ]

Secondary Outcome Measures:
  • Number of Participants with a Pathological Complete Response (pCR) [ Time Frame: Up to 27 weeks ]
  • Objective Response Rate (ORR) [ Time Frame: Up to 27 weeks ]

Estimated Enrollment: 100
Actual Study Start Date: January 27, 2016
Estimated Study Completion Date: June 16, 2018
Estimated Primary Completion Date: June 16, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A: KNp / KAC
Participants receive pembrolizumab (K) PLUS nab-paclitaxel (KNp) followed by pembrolizumab (K) PLUS doxorubicin (A) PLUS cyclophosphamide (C).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Nab-paclitaxel
IV infusion
Drug: Anthracycline (doxorubicin)
IV injection
Drug: Cyclophosphamide
IV infusion
Experimental: Cohort B: KNpCb / KAC Regimen 1
Participants receive Regimen 1 of pembrolizumab (K) PLUS nab-paclitaxel (KNp) PLUS carboplatin (Cb) followed by pembrolizumab (K) PLUS doxorubicin (A) PLUS cyclophosphamide (C).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Nab-paclitaxel
IV infusion
Drug: Anthracycline (doxorubicin)
IV injection
Drug: Cyclophosphamide
IV infusion
Drug: Carboplatin
IV infusion
Experimental: Cohort C: KNpCb / KAC Regimen 2
Participants receive Regimen 2 of pembrolizumab (K) PLUS nab-paclitaxel (KNp) PLUS carboplatin (Cb) followed by pembrolizumab (K) PLUS doxorubicin (A) PLUS cyclophosphamide (C).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Nab-paclitaxel
IV infusion
Drug: Anthracycline (doxorubicin)
IV injection
Drug: Cyclophosphamide
IV infusion
Drug: Carboplatin
IV infusion
Experimental: Cohort D: KNpCb / KAC Regimen 3
Participants receive Regimen 3 of pembrolizumab (K) PLUS nab-paclitaxel (KNp) PLUS carboplatin (Cb) followed by pembrolizumab (K) PLUS doxorubicin (A) PLUS cyclophosphamide (C).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Nab-paclitaxel
IV infusion
Drug: Anthracycline (doxorubicin)
IV injection
Drug: Cyclophosphamide
IV infusion
Drug: Carboplatin
IV infusion
Experimental: Cohort E: KTCb / KAC Regimen 1
Participants receive Regimen 1 of pembrolizumab (K) PLUS paclitaxel (T) PLUS carboplatin (Cb), followed by pembrolizumab (K) PLUS doxorubicin (A) PLUS cyclophosphamide (C).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Anthracycline (doxorubicin)
IV injection
Drug: Cyclophosphamide
IV infusion
Drug: Carboplatin
IV infusion
Drug: Paclitaxel
IV infusion
Experimental: Cohort F: KTCb / KAC Regimen 2
Participants receive Regimen 2 of pembrolizumab (K) PLUS paclitaxel (T) PLUS carboplatin (Cb) followed by pembrolizumab (K) + doxorubicin (A) PLUS cyclophosphamide (C).
Biological: Pembrolizumab
IV infusion
Other Names:
  • MK-3475
  • KEYTRUDA®
Drug: Anthracycline (doxorubicin)
IV injection
Drug: Cyclophosphamide
IV infusion
Drug: Carboplatin
IV infusion
Drug: Paclitaxel
IV infusion

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 120 days after the last dose of study drug.
  • Has a known hypersensitivity to the components of the study drug or its analogs.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02622074

Contacts
Contact: Toll Free Number 1-888-577-8839

Locations
Denmark
Merck Sharp & Dohme Recruiting
Glostrup, Denmark
Contact: Nathan Lassota    45 44824475      
Finland
MSD Finland Oy Recruiting
Espoo, Finland
Contact: Michael Pasternack    358 20 7570300      
Germany
MSD Sharp & Dohme GmbH Recruiting
Haar, Germany
Contact: German Medical Information Center    49 800 673 673 673      
Korea, Republic of
MSD Korea LTD Recruiting
Seoul, Korea, Republic of, 4130
Contact: Jongho Ahn    82-2-331-2000 2015      
Singapore
Merck Sharp & Dohme (I.A.) Corp Recruiting
Singapore, Singapore
Contact: Cesar Recto    632 784 9500      
Spain
Merck Sharp and Dohme de Espana S.A. Recruiting
Madrid, Spain
Contact: Joaquin Mateos Chacon    (0034) 913210600      
Sweden
MSD Sweden Recruiting
Stockholm, Sweden
Contact: Tryggve Ljung    46 (0)70 545 28 66      
United Kingdom
Merck Sharp & Dohme Ltd. Recruiting
Hoddesdon, United Kingdom
Contact: Mark Toms    +44 (0) 1992 452475      
Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.
  More Information

Additional Information:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02622074     History of Changes
Other Study ID Numbers: 3475-173
2015-002405-11 ( EudraCT Number )
Study First Received: December 2, 2015
Last Updated: August 18, 2017

Keywords provided by Merck Sharp & Dohme Corp.:
PD1
PD-1
PDL1
PD-L1
Triple Negative Breast Cancer

Additional relevant MeSH terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Liposomal doxorubicin
Pembrolizumab
Albumin-Bound Paclitaxel
Cyclophosphamide
Carboplatin
Doxorubicin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 21, 2017