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)

NCT ID: NCT02622074

Last Updated: 2020-09-10

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-01-27

Study Completion Date

2019-11-18

Brief Summary

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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).

Detailed Description

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Conditions

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Triple Negative Breast Neoplasms

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

200 mg administered Q3W as an IV infusion.

Nab-paclitaxel

Intervention Type DRUG

125 mg/m\^2 or 100 mg/m\^2 administered weekly as an IV infusion, according to allocation.

Anthracycline (doxorubicin)

Intervention Type DRUG

60 mg/m\^2 administered Q3W as an IV injection.

Cyclophosphamide

Intervention Type DRUG

600 mg/m\^2 administered Q3W as an IV infusion.

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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

200 mg administered Q3W as an IV infusion.

Nab-paclitaxel

Intervention Type DRUG

125 mg/m\^2 or 100 mg/m\^2 administered weekly as an IV infusion, according to allocation.

Anthracycline (doxorubicin)

Intervention Type DRUG

60 mg/m\^2 administered Q3W as an IV injection.

Cyclophosphamide

Intervention Type DRUG

600 mg/m\^2 administered Q3W as an IV infusion.

Carboplatin

Intervention Type DRUG

AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.

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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

200 mg administered Q3W as an IV infusion.

Nab-paclitaxel

Intervention Type DRUG

125 mg/m\^2 or 100 mg/m\^2 administered weekly as an IV infusion, according to allocation.

Anthracycline (doxorubicin)

Intervention Type DRUG

60 mg/m\^2 administered Q3W as an IV injection.

Cyclophosphamide

Intervention Type DRUG

600 mg/m\^2 administered Q3W as an IV infusion.

Carboplatin

Intervention Type DRUG

AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.

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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

200 mg administered Q3W as an IV infusion.

Nab-paclitaxel

Intervention Type DRUG

125 mg/m\^2 or 100 mg/m\^2 administered weekly as an IV infusion, according to allocation.

Anthracycline (doxorubicin)

Intervention Type DRUG

60 mg/m\^2 administered Q3W as an IV injection.

Cyclophosphamide

Intervention Type DRUG

600 mg/m\^2 administered Q3W as an IV infusion.

Carboplatin

Intervention Type DRUG

AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.

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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

200 mg administered Q3W as an IV infusion.

Anthracycline (doxorubicin)

Intervention Type DRUG

60 mg/m\^2 administered Q3W as an IV injection.

Cyclophosphamide

Intervention Type DRUG

600 mg/m\^2 administered Q3W as an IV infusion.

Carboplatin

Intervention Type DRUG

AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.

Paclitaxel

Intervention Type DRUG

80 mg/m\^2 or 70 mg/m\^2 administered weekly as an IV infusion, according to allocation.

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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

200 mg administered Q3W as an IV infusion.

Anthracycline (doxorubicin)

Intervention Type DRUG

60 mg/m\^2 administered Q3W as an IV injection.

Cyclophosphamide

Intervention Type DRUG

600 mg/m\^2 administered Q3W as an IV infusion.

Carboplatin

Intervention Type DRUG

AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.

Paclitaxel

Intervention Type DRUG

80 mg/m\^2 or 70 mg/m\^2 administered weekly as an IV infusion, according to allocation.

Interventions

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Pembrolizumab

200 mg administered Q3W as an IV infusion.

Intervention Type BIOLOGICAL

Nab-paclitaxel

125 mg/m\^2 or 100 mg/m\^2 administered weekly as an IV infusion, according to allocation.

Intervention Type DRUG

Anthracycline (doxorubicin)

60 mg/m\^2 administered Q3W as an IV injection.

Intervention Type DRUG

Cyclophosphamide

600 mg/m\^2 administered Q3W as an IV infusion.

Intervention Type DRUG

Carboplatin

AUC 6 or AUC5 administered Q3W as an IV infusion, or AUC2 administered weekly as an IV infusion, according to allocation.

Intervention Type DRUG

Paclitaxel

80 mg/m\^2 or 70 mg/m\^2 administered weekly as an IV infusion, according to allocation.

Intervention Type DRUG

Other Intervention Names

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MK-3475 KEYTRUDA®

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

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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.

Reference Type RESULT
PMID: 32278621 (View on PubMed)

Dent 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.

Reference Type DERIVED
PMID: 40069763 (View on PubMed)

Perez-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.

Reference Type DERIVED
PMID: 32450725 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trial Information

Other Identifiers

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2015-002405-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-3475-173

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-173

Identifier Type: OTHER

Identifier Source: secondary_id

3475-173

Identifier Type: -

Identifier Source: org_study_id

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