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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)

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ClinicalTrials.gov Identifier: NCT02622074
Recruitment Status : Active, not recruiting
First Posted : December 4, 2015
Last Update Posted : May 15, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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).

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 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 Type : Interventional  (Clinical Trial)
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 : January 27, 2016
Estimated Primary Completion Date : June 16, 2018
Estimated Study Completion Date : November 4, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
U.S. FDA Resources

Arm Intervention/treatment
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



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

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


Information from the National Library of Medicine

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, Learn About Clinical Studies.


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02622074


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

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 )
MK-3475-173 ( Other Identifier: Merck Protocol Number )
First Posted: December 4, 2015    Key Record Dates
Last Update Posted: May 15, 2018
Last Verified: May 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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