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

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 213363
  • SECONDARY ID: 3000-PN162-01-001
  • NCT ID: NCT02657889

Conditions

  • Neoplasms
  • Triple Negative Breast Cancer
  • Ovarian Cancer
  • Breast Cancer
  • Metastatic Breast Cancer
  • Advanced Breast Cancer
  • Stage IV Breast Cancer
  • Fallopian Tube Cancer
  • Peritoneal Cancer

Interventions

DrugSynonymsArms
niraparibniraparib plus pembrolizumab
pembrolizumabniraparib plus pembrolizumab

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)

Trial Arms

NameTypeDescriptionInterventions
niraparib plus pembrolizumabExperimentalPhase 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
  • pembrolizumab

Eligibility Criteria

        Main Inclusion Criteria:

          -  Patient has histologically proven advanced (unresectable) or metastatic cancer as
             outlined below according to study phase and disease type:

               1. Phase 1 patients (breast or ovarian cancer)

                    -  Patients with advanced or metastatic breast cancer must have disease that is
                       HER2-negative, estrogen receptor-negative, and progesterone
                       receptor-negative (ie, TNBC). Patients with advanced or metastatic disease
                       may have up to 4 lines of cytotoxic therapy. Neoadjuvant and adjuvant
                       therapies are not counted towards lines of therapy.

                    -  Patients must have any epithelial (ie, serous, endometroid, mucinous, clear
                       cell) ovarian, fallopian tube, or primary peritoneal cancer. Patients must
                       have experienced a response lasting at least 6 months to first-line
                       platinum-based therapy but currently considered to have platinum-resistant
                       disease per investigator's assessment (e.g, patient is not eligible for
                       further platinum containing treatment). Patients may have received up to 5
                       lines of cytotoxic therapy for advanced or metastatic cancer. Neoadjuvant
                       and adjuvant therapies are not counted towards lines of therapy.

               2. Phase 2 patients (breast or ovarian cancer)

                    -  Patients with advanced or metastatic breast cancer must have TNBC. Patients
                       with advanced or metastatic disease may have received up to 2 lines of
                       cytotoxic therapy. Adjuvant and/or neoadjuvant therapies are not counted in
                       the number of lines of therapy. TNBC patients who have previously received
                       platinum chemotherapy in the metastatic setting are allowed to enroll in the
                       study as long as they did not progress while on or within 8 weeks from the
                       day of the last platinum administration.

                    -  Patients must have with high-grade serous or endometroid ovarian, fallopian
                       tube, or primary peritoneal cancer. Patients must have experienced a
                       response lasting at least 6 months to first-line platinum-based therapy but
                       currently considered to have platinum-resistant disease per investigator's
                       assessment (e.g, patient is not eligible for further platinum containing
                       treatment). Patients may have had up to 4 lines of cytotoxic therapy for
                       advanced or metastatic cancer. Neoadjuvant, adjuvant, and the combination of
                       both will be considered as one line of therapy.

          -  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:

          -  Patients with primary platinum refractory ovarian cancer (ie, progressive disease on
             or within 6 months of first-line platinum 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 2 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

          -  Condition (such as transfusion dependent anemia or thrombocytopenia), therapy, or
             laboratory abnormality that might confound the study results, or interfere with the
             patient's participation for the full duration of the study treatment.

          -  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

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

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

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

          -  Known history or current diagnosis of myelodysplastic syndrome (MDS) or acute myeloid
             leukemia (AML)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1: Number of Subjects Reporting Dose-Limiting Toxicities (DLTs)
Time Frame:During Cycle 1, ie, during the first 21 days of treatment
Safety Issue:
Description:DLTs are defined as: Any treatment-related Grade ≥ 3 non-hematologic clinical (non-laboratory) AE Any treatment-related Grade 3 or Grade 4 non-hematologic lab abnormality if: - Medical intervention is required to treat the patient, or - The abnormality leads to hospitalization, or - The abnormality persists for ≥ 7 days. Any treatment-related hematologic toxicity specifically defined as: - Thrombocytopenia Grade 4 for ≥ 7 days, or Grade 3 or 4 associated with bleeding or requiring platelet transfusion; - Neutropenia Grade 4 for ≥ 7 days, or Grade 3 or 4 associated with infection or febrile neutropenia; - Anemia Grade 4, or Grade 3 or 4 requiring blood transfusion. Any treatment-related AE leading to niraparib dose interruption per the following criteria: - A dose interruption for a non-DLT lab abnormality lasting ≥ 14 days. - A dose in interruption per dose modification rules for nonhematologic AE leading to < 80% of an intended dose being administered.

Secondary Outcome Measures

Measure: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:AEs were collected up to 90 days following the last dose of study treatment, where the median duration of treatment was 3 months.
Safety Issue:
Description:Percentage of patients with at least 1 Treatment-Emergent Adverse Event. Refer to the adverse event tables for specific details.
Measure:Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST)
Time Frame:Radiographic evaluations were conducted every 9 weeks while on study treatment (every 12 weeks after 1 year of scans) independent of cycle delays and/or dose interruptions, and/or at any time when progression of disease is suspected.
Safety Issue:
Description:ORR by irRECIST is defined as the proportion of patients who achieved a best overall response of complete response (CR) or partial response (PR) using immune-related RECIST criteria.
Measure:Phase 2: Duration of Response (DOR)
Time Frame:From first documentation of response (CR or PR) using RECIST (v1.1) as assessed by the Investigator until time of first documented progression.
Safety Issue:
Description:From first documentation of response (CR or PR) using RECIST (v1.1) as assessed by the investigator until time of first documented progression or death by any cause. No maximum timeframe was specified in the protocol.
Measure:Phase 2: Disease Control Rate (DCR)
Time Frame:Up to 40 weeks
Safety Issue:
Description:DCR is defined as the percentage of patients who achieved a CR or PR or stable disease (SD) using RECIST (v1.1) as assessed by the Investigator.
Measure:Phase 2: Progression Free Survival (PFS)
Time Frame:From date of first dose to the earlier date of assessment of progression of death by any cause in the absence of progression.
Safety Issue:
Description:From date of first dose to the earlier date of assessment of progression or death by any cause in the absence of progression. No maximum timeframe was specified in the protocol.
Measure:Phase 2: Overall Survival (OS)
Time Frame:From date of first dose to the date of death by any cause.
Safety Issue:
Description:Patients were followed off treatment every 90 days for survival status. Overall survival is defined as the time from first dose to the date of death by any cause. No maximum timeframe was specified in the protocol.
Measure:Phase 1 and Phase 2: To Evaluate the Pharmacokinetics (PK) of Niraparib and Associated Major Metabolite M1 During Combination Treatment.
Time Frame:Approximately 9 months
Safety Issue:
Description: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).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Tesaro, Inc.

Trial Keywords

  • PARP inhibitor
  • PD-1
  • Niraparib
  • Pembrolizumab
  • Keynote
  • TOPACIO

Last Updated

June 11, 2021