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Trial record 1 of 1 for:    NCT02819518
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Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (MK-3475-355/KEYNOTE-355)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02819518
Recruitment Status : Active, not recruiting
First Posted : June 30, 2016
Last Update Posted : October 28, 2019
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE June 28, 2016
First Posted Date  ICMJE June 30, 2016
Last Update Posted Date October 28, 2019
Actual Study Start Date  ICMJE July 27, 2016
Estimated Primary Completion Date December 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 24, 2019)
  • Part 1: Percentage of Participants Who Experience an Adverse Event (AE) - All Participants [ Time Frame: Up to 45 months ]
  • Part 1: Percentage of Participants Who Discontinue Study Drug Due to an AE - All Participants [ Time Frame: Up to 45 months ]
  • Part 2: Progression-Free Survival (PFS) - All Participants [ Time Frame: Up to 45 months ]
  • Part 2: PFS - Participants with Programmed Cell Death-Ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: PFS - Participants with PD-L1 CPS ≥10 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: Overall Survival (OS) - All Participants [ Time Frame: Up to 45 months ]
  • Part 2: OS - Participants with PD-L1 CPS ≥1 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: OS - Participants with PD-L1 CPS ≥10 Tumors [ Time Frame: Up to 45 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: June 28, 2016)
  • Part 1: Percentage of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to 44 months ]
  • Part 1: Percentage of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to 41 months ]
  • Part 2: Progression-Free Survival (PFS) - All Participants [ Time Frame: Up to 41 months ]
  • Part 2: PFS - Participants With PD-L1 Positive Tumors [ Time Frame: Up to 41 months ]
  • Part 2: Overall Survival (OS) - All Participants [ Time Frame: Up to 41 months ]
  • Part 2: OS - Participants With PD-L1 Positive Tumors [ Time Frame: Up to 41 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 24, 2019)
  • Part 2: Objective Response Rate (ORR) - All Participants [ Time Frame: Up to 45 months ]
  • Part 2: ORR - Participants With PD-L1 CPS ≥1 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: ORR - Participants With PD-L1 CPS ≥10 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: Duration of Response (DOR) - All Participants [ Time Frame: Up to 45 months ]
  • Part 2: DOR - Participants With PD-L1 CPS ≥1 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: DOR - Participants With PD-L1 CPS ≥10 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: Disease Control Rate (DCR) - All Participants [ Time Frame: Up to 45 months ]
  • Part 2: DCR - Participants With PD-L1 CPS ≥1 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: DCR - Participants With PD-L1 CPS ≥10 Tumors [ Time Frame: Up to 45 months ]
  • Part 2: Percentage of Participants Who Experience an AE- All Participants [ Time Frame: Up to 45 months ]
  • Part 2: Percentage of Participants Who Discontinue Study Drug Due to an AE- All Participants [ Time Frame: Up to 45 months ]
  • Part 2: Change from Baseline to End of Study in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Total Score - All Participants [ Time Frame: Baseline and End of Study Participation (Up 45 months) ]
  • Part 2: Change from Baseline to End of Study in EORTC QLQ-C30 Total Score - Participants With PD-L1 CPS ≥1 Tumors [ Time Frame: Baseline and End of Study Participation (Up 45 months) ]
  • Part 2: Change from Baseline to End of Study in EORTC QLQ-C30 Total Score - Participants With PD-L1 CPS ≥10 Tumors [ Time Frame: Baseline and End of Study Participation (Up 45 months) ]
  • Part 2: Change from Baseline to End of Study in EORTC Breast Cancer-Specific Quality of Life Questionnaire (QLQ-BR23) Total Score - All Participants [ Time Frame: Baseline and End of Study Participation (Up 45 months) ]
  • Part 2: Change from Baseline to End of Study in EORTC QLQ-BR23 Total Score - Participants with PD-L1 CPS ≥1 Tumors [ Time Frame: Baseline and End of Study Participation (Up 45 months) ]
  • Part 2: Change from Baseline to End of Study in EORTC QLQ-BR23 Total Score - Participants with PD-L1 CPS ≥10 Tumors [ Time Frame: Baseline and End of Study Participation (Up 45 months) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 28, 2016)
  • Part 2: Objective Response Rate (ORR) - All Participants [ Time Frame: Up to 41 months ]
  • Part 2: ORR - Participants With PD-L1 Positive Tumors [ Time Frame: Up to 41 months ]
  • Part 2: Duration of Response (DOR) - All Participants [ Time Frame: Up to 41 months ]
  • Part 2: DOR - Participants With PD-L1 Positive Tumors [ Time Frame: Up to 41 months ]
  • Part 2: Disease Control Rate (DCR) - All Participants [ Time Frame: Up to 41 months ]
  • Part 2: DCR - Participants With PD-L1 Positive Tumors [ Time Frame: Up to 41 months ]
  • Part 2: Percentage of Participants Who Experience an AE [ Time Frame: Up to 44 months ]
  • Part 2: Percentage of Participants Who Discontinue Study Drug Due to an AE [ Time Frame: Up to 41 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs. Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer (MK-3475-355/KEYNOTE-355)
Official Title  ICMJE A Randomized, Double-Blind, Phase III Study of Pembrolizumab (MK-3475) Plus Chemotherapy vs Placebo Plus Chemotherapy for Previously Untreated Locally Recurrent Inoperable or Metastatic Triple Negative Breast Cancer - (KEYNOTE-355)
Brief Summary

The study will consist of two parts.

In Part 1, the safety of pembrolizumab (MK-3475) in combination with one of three different chemotherapies will be assessed in the treatment of locally recurrent inoperable or metastatic triple negative breast cancer (TNBC), which has not been previously treated with chemotherapy.

In Part 2, the safety and efficacy of pembrolizumab plus chemotherapy will be assessed compared to the safety and efficacy of placebo plus chemotherapy in the treatment of locally recurrent inoperable or metastatic TNBC, which has not been previously treated with chemotherapy.

The primary hypotheses are that:

  1. the combination of pembrolizumab and chemotherapy prolongs Progression-Free Survival (PFS) compared to placebo and chemotherapy in:

    • all participants,
    • participants with programmed cell death-ligand 1 (PD-L1) combined positive score (CPS) ≥1 tumors, and
    • participants with PD-L1 CPS ≥10 tumors, and
  2. the combination of pembrolizumab and chemotherapy prolongs Overall Survival (OS) compared to placebo and chemotherapy in:

    • all participants,
    • participants with PD-L1 CPS ≥1 tumors, and
    • participants with PD-L1 CPS ≥10 tumors.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Triple Negative Breast Cancer (TNBC)
Intervention  ICMJE
  • Biological: Pembrolizumab
    IV infusion
    Other Names:
    • MK-3475
    • KEYTRUDA®
  • Drug: Nab-paclitaxel
    IV infusion
    Other Name: ABRAXANE®
  • Drug: Paclitaxel
    IV infusion
    Other Name: TAXOL®
  • Drug: Gemcitabine
    IV infusion
    Other Name: GEMZAR®
  • Drug: Carboplatin
    IV infusion
    Other Name: PARAPLATIN®
  • Drug: Normale Saline Solution
    IV infusion
Study Arms  ICMJE
  • Experimental: Part 1: Pembrolizumab + Nab-paclitaxel
    Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Nab-paclitaxel
  • Experimental: Part 1: Pembrolizumab + Paclitaxel
    Participants receive pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Paclitaxel
  • Experimental: Part 1: Pembrolizumab + Gemcitabine/Carboplatin
    Participants receive pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an Area Under the Curve (AUC) 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Gemcitabine
    • Drug: Carboplatin
  • Experimental: Part 2: Pembrolizumab + Chemotherapy
    Participants receive pembrolizumab 200 mg IV on Day 1 of each 21-day cycle PLUS one of three chemotherapy regimens: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Nab-paclitaxel
    • Drug: Paclitaxel
    • Drug: Gemcitabine
    • Drug: Carboplatin
  • Active Comparator: Part 2: Placebo + Chemotherapy
    Participants receive placebo (normal saline) IV on Day 1 of each 21-day cycle PLUS one of three chemotherapy regimens: 1) nab-paclitaxel 100 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, 2) paclitaxel 90 mg/m^2 IV on Days 1, 8 and 15 of each 28-day cycle, OR 3) gemcitabine/carboplatin 1000 mg/m^2 (gemcitabine) and an AUC 2 (carboplatin) on Days 1 and 8 of each 21-day cycle.
    Interventions:
    • Drug: Nab-paclitaxel
    • Drug: Paclitaxel
    • Drug: Gemcitabine
    • Drug: Carboplatin
    • Drug: Normale Saline Solution
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 24, 2019)
882
Original Estimated Enrollment  ICMJE
 (submitted: June 28, 2016)
858
Estimated Study Completion Date  ICMJE December 30, 2019
Estimated Primary Completion Date December 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has locally recurrent inoperable breast cancer not previously treated with chemotherapy and which cannot be treated with curative intent OR has metastatic breast cancer not previously treated with chemotherapy.
  • Has centrally confirmed TNBC, as defined by the most recent American Society of Clinical Oncology/college of American Pathologists (ASCO/CAP) guidelines.
  • Has completed treatment for Stage I-III breast cancer, if indicated, and ≥6 months elapsed between the completion of treatment with curative intent (e.g., date of primary breast tumor surgery or date of last adjuvant chemotherapy administration, whichever occurred last) and first documented local or distant disease recurrence.
  • Has been treated with (neo)adjuvant anthracycline, if they received systemic treatment in the (neo)adjuvant setting, unless anthracycline was contraindicated or not considered the best treatment option for the participant in the opinion of the treating physician.
  • Has measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by local radiology review.
  • Has provided recently or newly obtained core or excisional biopsy from a locally recurrent inoperable or metastatic tumor lesion for central determination of TNBC status and PD-L1 expression, unless contraindicated due to site inaccessibility and/or participant safety concerns.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as assessed within 10 days prior to the start of study drug.
  • Has a life expectancy ≥12 weeks from randomization.
  • Demonstrates adequate organ function, within 10 days prior to the start of study drug.
  • Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 120 days (or longer as specified by local institutional guidelines) after the last dose of study drug.
  • Male participants of childbearing potential must agree to use an adequate method of contraception starting with the first dose of study drug through 120 days (or longer as specified by local institutional guidelines) after the last dose of study drug.

Exclusion Criteria:

  • Is currently participating in a clinical study and receiving an investigational agent and/or using an investigational device, or has participated in a clinical study and received an investigational agent and/or used an investigational device within 4 weeks prior to randomization.
  • Has not recovered (e.g., to ≤ Grade 1 or to baseline) from AEs due to a previously administered therapy.
  • Has neuropathy ≥ Grade 2.
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years (e.g., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization.
  • Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer.
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable brain metastases and did not receive chemotherapy for metastatic breast cancer.
  • Has history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  • Has active, or a history of, interstitial lung disease.
  • Has a known history of active tuberculosis (TB).
  • Has an active infection requiring systemic therapy.
  • Has a history of Class II-IV congestive heart failure or myocardial infarction within 6 months of randomization.
  • Has a 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 or father children within the projected duration of the study, starting with the screening visit through 120 days (or longer as specified by local institutional guidelines) after the last dose of study drug.
  • Has received prior therapy with an anti-programmed cell death 1 (anti-PD-1), anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T cell receptor (such as cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, CD137) or has previously participated in Merck pembrolizumab (MK-3475) clinical studies.
  • Has a known history of human immunodeficiency virus (HIV).
  • Has known active hepatitis B or hepatitis C.
  • Has received a live vaccine within 30 days prior to randomization.
  • Has a known history of hypersensitivity or allergy to pembrolizumab and any of its components and/or to any of the study chemotherapies (e.g., nab-paclitaxel, paclitaxel, gemcitabine, or carboplatin) and any of their components.
  • Is receiving any medication prohibited in combination with study chemotherapies as described in the respective product labels, unless medication was stopped within 7 days prior to randomization.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries Argentina,   Australia,   Austria,   Belgium,   Brazil,   Canada,   Chile,   Colombia,   Czech Republic,   Czechia,   Denmark,   Finland,   France,   Germany,   Hong Kong,   Hungary,   Ireland,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Netherlands,   New Zealand,   Poland,   Russian Federation,   Spain,   Taiwan,   Turkey,   Ukraine,   United Kingdom,   United States
 
Administrative Information
NCT Number  ICMJE NCT02819518
Other Study ID Numbers  ICMJE 3475-355
2016-001432-35 ( EudraCT Number )
163422 ( Registry Identifier: JAPAN-CTI )
MK-3475-355 ( Other Identifier: Merck )
KEYNOTE-355 ( Other Identifier: Merck )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP