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Study of Niraparib in Combination With Pembrolizumab (MK-3475) in Patients With Triple-negative Breast Cancer or Ovarian Cancer (TOPACIO)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Tesaro, Inc.
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Tesaro, Inc. Identifier:
First received: January 8, 2016
Last updated: February 21, 2017
Last verified: August 2016
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)

Condition Intervention Phase
Triple Negative Breast Cancer
Ovarian Cancer
Breast Cancer
Metastatic Breast Cancer
Advanced Breast Cancer
Stage IV Breast Cancer
Fallopian Tube Cancer
Peritoneal Cancer
Drug: niraparib
Biological: pembrolizumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Tesaro, Inc.:

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 [ Time Frame: Phase 1: Approximately 9 months ]
  • 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 [ Time Frame: Phase 2: Approximately 12 months ]

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) [ Time Frame: Approximately 18 months ]
  • Overall Response Rate (ORR) [ Time Frame: Approximately 12 months ]
    as measured by immune-related RECIST (irRECIST)

  • Duration of Response (DOR) [ Time Frame: Approximately 18 months ]
    defined as the time from first documentation of response (CR or PR) until the time of first documentation of disease progression

  • Disease Control Rate (DCR) [ Time Frame: Approximately 12 months ]
    defined as the percentage of patients who have achieved CR, PR, or stable disease (SD) per RECIST or irRECIST

  • Progression Free Survival (PFS) [ Time Frame: Approximately 18 months ]
    defined as the time from first dose to the earlier date of assessment of progression, or death by any cause in the absence of progression, by RECIST or irRECIST

  • Overall Survival (OS) [ Time Frame: Approximately 2 years ]
    as measured from the date of first dose to the date of death by any cause

  • To evaluate the Area Under the Curve (AUC), Minimum concentration (Cmin) [ Time Frame: Approximately 9 months ]
  • Maximum Concentration (Cmax) [ Time Frame: Approximately 9 months ]
  • Clearance after oral administration (CL/F) [ Time Frame: Approximately 9 months ]
  • Volume of Distribution after oral administration (Vz/F) [ Time Frame: Approximately 9 months ]
  • AUC at steady state (AUCss) [ Time Frame: Approximately 9 months ]
  • Cmin at steady state (Cmin,ss) [ Time Frame: Approximately 9 months ]
    and Cmax at steady state (Cmax,ss)

  • Cmax at steady state (Cmax,ss) [ Time Frame: Approximately 9 months ]

Estimated Enrollment: 114
Study Start Date: March 2016
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: niraparib plus pembrolizumab

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

Drug: niraparib Biological: pembrolizumab


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02657889

Contact: Clinical Trial Management Group

United States, Arizona
Scottsdale, Arizona, United States, 85258
Contact: Joyce Schaffer    480-323-1339   
United States, Massachusetts
Boston, Massachusetts, United States, 02215
Contact: Panos Konstantinopoulos, MD, PhD    617-632-2334   
United States, Ohio
Cleveland, Ohio, United States, 44106
Contact: Cancer Information Services    800-641-2422      
United States, Oklahoma
Oklahoma City, Oklahoma, United States, 73104
Contact: Ingrid Block    405-271-8777   
United States, Tennessee
Germantown, Tennessee, United States, 38138
Contact: Cindy Inman    901-683-0055 ext 61236   
Sponsors and Collaborators
Tesaro, Inc.
Merck Sharp & Dohme Corp.
Study Director: Bruce Dezube, MD Tesaro, Inc.
  More Information

Responsible Party: Tesaro, Inc. Identifier: NCT02657889     History of Changes
Other Study ID Numbers: 3000-PN162-01-001
Study First Received: January 8, 2016
Last Updated: February 21, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Tesaro, Inc.:
PARP inhibitor

Additional relevant MeSH terms:
Breast Neoplasms
Ovarian Neoplasms
Fallopian Tube Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Fallopian Tube Diseases
Antineoplastic Agents
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action processed this record on March 28, 2017