Clinical Trials /

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)

NCT02819518

Description:

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 the combination of pembrolizumab and chemotherapy prolongs Progression-Free Survival (PFS) compared to placebo and chemotherapy in all participants and in participants with programmed cell death-ligand 1 (PD-L1) positive tumors, and prolongs Overall Survival (OS) compared to placebo and chemotherapy in all participants and in participants with PD-L1 positive tumors.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: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: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)

Clinical Trial IDs

  • ORG STUDY ID: 3475-355
  • SECONDARY ID: 2016-001432-35
  • NCT ID: NCT02819518

Trial Conditions

  • Triple Negative Breast Cancer (TNBC)

Trial Interventions

DrugSynonymsArms
Nab-paclitaxelABRAXANE®Part 1: Pembrolizumab + Nab-paclitaxel
PaclitaxelTAXOL®Part 1: Pembrolizumab + Paclitaxel
GemcitabineGEMZAR®Part 1: Pembrolizumab + Gemcitabine/Carboplatin
CarboplatinPARAPLATIN®Part 1: Pembrolizumab + Gemcitabine/Carboplatin
Normale Saline SolutionPart 2: Placebo + Chemotherapy

Trial Purpose

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 the combination of pembrolizumab and chemotherapy prolongs Progression-Free Survival (PFS) compared to placebo and chemotherapy in all participants and in participants with programmed cell death ligand 1 (PD-L1) positive tumors, and prolongs Overall Survival (OS) compared to placebo and chemotherapy in all participants and in participants with PD-L1 positive tumors.

Detailed Description

Prior treatment with chemotherapy in the (neo)adjuvant setting is allowed. For such participants, the period between 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 must be ≥6 months. Participants who received taxane, gemcitabine, or platinum agents in the (neo)adjuvant setting can be treated with same class anticancer drug (taxane, gemcitabine, or carboplatin, respectively), if ≥12 months have elapsed between completion of treatment with curative intent and the first documented local or distant disease recurrence.

Trial Arms

NameTypeDescriptionInterventions
Part 1: Pembrolizumab + Nab-paclitaxelExperimentalParticipants 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.
    • Nab-paclitaxel
    Part 1: Pembrolizumab + PaclitaxelExperimentalParticipants 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.
        • Paclitaxel
      Part 1: Pembrolizumab + Gemcitabine/CarboplatinExperimentalParticipants 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.
            • Gemcitabine
            • Carboplatin
        Part 2: Pembrolizumab + ChemotherapyExperimentalParticipants 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.
          • Nab-paclitaxel
          • Paclitaxel
          • Gemcitabine
          • Carboplatin
          Part 2: Placebo + ChemotherapyActive ComparatorParticipants 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.
            • Nab-paclitaxel
            • Paclitaxel
            • Gemcitabine
            • Carboplatin
            • Normale Saline Solution

          Eligibility Criteria

          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 active, or a history of, pneumonitis requiring treatment with steroids.

          - 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.

          Maximum Eligible Age:N/A
          Minimum Eligible Age:18 Years
          Eligible Gender:Both
          Healthy Volunteers:No

          Primary Outcome Measures

          Measure:Part 1: Percentage of Participants Who Experience an Adverse Event (AE)
          Time Frame:Up to 44 months
          Safety Issue:Yes
          Description:

          Secondary Outcome Measures

          Measure:Part 2: Objective Response Rate (ORR) - All Participants
          Time Frame:Up to 41 months
          Safety Issue:No
          Description:
          Measure:Part 2: ORR - Participants With PD-L1 Positive Tumors
          Time Frame:Up to 41 months
          Safety Issue:No
          Description:
          Measure:Part 2: Duration of Response (DOR) - All Participants
          Time Frame:Up to 41 months
          Safety Issue:No
          Description:
          Measure:Part 2: DOR - Participants With PD-L1 Positive Tumors
          Time Frame:Up to 41 months
          Safety Issue:No
          Description:
          Measure:Part 2: Disease Control Rate (DCR) - All Participants
          Time Frame:Up to 41 months
          Safety Issue:No
          Description:
          Measure:Part 2: DCR - Participants With PD-L1 Positive Tumors
          Time Frame:Up to 41 months
          Safety Issue:No
          Description:
          Measure:Part 2: Percentage of Participants Who Experience an AE
          Time Frame:Up to 44 months
          Safety Issue:Yes
          Description:
          Measure:Part 2: Percentage of Participants Who Discontinue Study Drug Due to an AE
          Time Frame:Up to 41 months
          Safety Issue:Yes
          Description:

          Trial Keywords

          • PD1
          • PD-1
          • PDL1
          • PD-L1