Clinical Trials /

Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer

NCT02657889

Description:

This Phase 1/2 study will evaluate the safety and efficacy of combination treatment with niraparib and pembrolizumab (MK-3475) in patients with advanced or metastatic triple-negative breast cancer or recurrent ovarian cancer. (KEYNOTE-162)

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Study of <span class="go-doc-concept go-doc-intervention">Niraparib</span> in Combination With <span class="go-doc-concept go-doc-intervention">Pembrolizumab (MK-3475)</span> in Patients With <span class="go-doc-concept go-doc-keyword">Triple-negative</span> Breast Cancer or Ovarian Cancer (KEYNOTE-162)

Title

  • Brief Title: Study of Niraparib in Combination With Pembrolizumab (MK-3475) in Patients With Triple-negative Breast Cancer or Ovarian Cancer (KEYNOTE-162)
  • Official Title: Phase 1/2 Clinical Study of Niraparib in Combination With Pembrolizumab in Patients With Advanced or Metastatic Triple-Negative Breast Cancer and in Patients With Recurrent Ovarian Cancer
  • Clinical Trial IDs

    NCT ID: NCT02657889

    ORG ID: 3000-PN162-01-001

    Trial Conditions

    Triple Negative Breast Cancer

    Ovarian Cancer

    Breast Cancer

    Metastatic Breast Cancer

    Advanced Breast Cancer

    Stage IV Breast Cancer

    Fallopian Tube Cancer

    Peritoneal Cancer

    Trial Interventions

    Drug Synonyms Arms
    niraparib niraparib plus pembrolizumab

    Trial Purpose

    This Phase 1/2 study will evaluate the safety and efficacy of combination treatment with
    niraparib and pembrolizumab (MK-3475) in patients with advanced or metastatic
    triple-negative breast cancer or recurrent ovarian cancer. (KEYNOTE-162)

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    niraparib plus pembrolizumab Experimental Phase 1: Dose-escalation: ascending doses of niraparib up to 300mg/day orally (PO) on Days 1-21 and pembrolizumab 200mg intravenously (IV) on Day 1 of each 21-day cycle Phase 2: niraparib (recommended Phase 2 dose) in combination with pembrolizumab 200mg IV on Day 1 of each 21-day cycle niraparib

    Eligibility Criteria

    Main Inclusion Criteria:

    - Histologically proven advanced (unresectable) or metastatic cancer as outlined below

    1. Patients with triple-negative breast cancer (TNBC) who have been treated with at
    least 1 prior regimen for advanced/metastatic disease or who relapsed/progressed
    while on or within 1 month from completion of adjuvant chemotherapy

    Phase 1: Up to 3 lines of prior chemotherapy are allowed

    Phase 2: Up to 2 lines of prior chemotherapy are allowed

    2. Patients with high-grade serous ovarian, fallopian tube, or primary peritoneal
    cancer who have recurrent disease and have been previously treated with
    chemotherapy for advanced/metastatic disease and who experienced a response
    lasting at least 6 months to first-line platinum-based therapy but currently
    considered platinum-resistant

    Phase 1: Up to 4 lines of prior chemotherapy are allowed

    Phase 2: Up to 3 lines of prior chemotherapy are allowed

    - Archival tumor tissue available or a fresh biopsy must be obtained prior to study
    treatment initiation

    - Measurable lesions by RECIST v1.1

    - Eastern Cooperative Oncology Group (ECOG) 0 or 1

    - Adequate organ function

    - Able to take oral medications

    - Female patient, if of childbearing potential, has a negative serum pregnancy test
    within 72 hours of taking study medication and agrees to abstain from activities that
    could result in pregnancy from enrollment through 120 days after the last dose of
    study treatment

    - Male patient agrees to use an adequate method of contraception

    Main Exclusion Criteria:

    - Progressed while on platinum treatment or within 1 month from completion of
    platinum-containing regimen in any line of therapy

    - Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
    Note: Patients previously treated for brain metastases may be able to participate
    provided they are stable

    - Patient 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, or in situ cervical cancer)

    - Poor medical risk

    - Pregnant or breastfeeding, or expecting to conceive children within the projected
    duration of the study

    - Immunodeficiency or is receiving systemic steroid therapy or any other form of
    immunosuppressive therapy within 7 days prior to the first dose of study treatment

    - Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)

    - Known active hepatitis B or hepatitis C

    - Active autoimmune disease that has required systemic treatment in the past 2 years
    (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive
    drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid
    replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
    form of systemic treatment

    - History of interstitial lung disease

    - Known history of platelet transfusion for chemotherapy-induced thrombocytopenia or
    persistent (> 4 weeks) Grade 3 hematological toxicity or fatigue from prior cancer
    therapy

    - Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2

    - Prior treatment with a known poly(ADP-ribose) polymerase (PARP) inhibitor

    - Heart-rate corrected QT interval (QTc) prolongation > 470 msec at screening

    - Known history of myelodysplastic syndrome (MDS) or a pre-treatment cytogenetic
    testing result at risk for a diagnosis of MDS/acute myeloid leukemia (AML)

    - Receiving concomitant medications that prolong QTc and is unable to discontinue use

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Evaluate dose-limiting toxicities (DLTs) of combination treatment with niraparib and pembrolizumab during the first cycle of treatment, and to establish a recommended Phase 2 dose (RP2D) and schedule

    To estimate the clinical activity of combination treatment with niraparib and pembrolizumab in terms of objective response rate (ORR) as assessed by the Investigators using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

    Secondary Outcome Measures

    To evaluate the safety and tolerability of combination treatment with niraparib and pembrolizumab using Common Terminology Criteria for Adverse Events (CTCAE, v4.03)

    Overall Response Rate (ORR)

    Duration of Response (DOR)

    Disease Control Rate (DCR)

    Progression Free Survival (PFS)

    Overall Survival (OS)

    To evaluate the Area Under the Curve (AUC), Minimum concentration (Cmin)

    Maximum Concentration (Cmax)

    Clearance after oral administration (CL/F)

    Volume of Distribution after oral administration (Vz/F)

    AUC at steady state (AUCss)

    Cmin at steady state (Cmin,ss)

    Cmax at steady state (Cmax,ss)

    Trial Keywords

    PARP inhibitor

    PD-1

    Niraparib

    Pembrolizumab

    Keynote