Niraparib in Combination With Pembrolizumab in Patients With Triple-negative Breast Cancer or Ovarian Cancer (TOPACIO)
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ClinicalTrials.gov Identifier: NCT02657889 |
Recruitment Status :
Active, not recruiting
First Posted : January 18, 2016
Results First Posted : February 11, 2020
Last Update Posted : January 13, 2021
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Condition or disease | Intervention/treatment | Phase |
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Neoplasms 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 (Clinical Trial) |
Actual Enrollment : | 122 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |
Actual Study Start Date : | March 9, 2016 |
Actual Primary Completion Date : | May 14, 2018 |
Estimated Study Completion Date : | April 30, 2021 |

Arm | Intervention/treatment |
---|---|
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 |
- Phase 1: Number of Subjects Reporting Dose-Limiting Toxicities (DLTs) [ Time Frame: During Cycle 1, ie, during the first 21 days of treatment ]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.
- Phase 2: Objective Response Rate (ORR) [ Time Frame: Up to 40 weeks ]ORR is defined as the percentage of patients who achieved a best overall response of Complete Response (CR) or Partial Response (PR), per Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1) for target lesions as assessed by the Investigator: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- 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. ]Percentage of patients with at least 1 Treatment-Emergent Adverse Event. Refer to the adverse event tables for specific details.
- 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. ]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.
- 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. ]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.
- Phase 2: Disease Control Rate (DCR) [ Time Frame: Up to 40 weeks ]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.
- 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. ]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.
- Phase 2: Overall Survival (OS) [ Time Frame: From date of first dose to the date of death by any cause. ]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.
- 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 ]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).

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Main Inclusion Criteria:
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Patient has histologically proven advanced (unresectable) or metastatic cancer as outlined below according to study phase and disease type:
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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.
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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.
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- 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)

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02657889

Study Director: | GSK Clinical Trials | GlaxoSmithKline |
Documents provided by Tesaro, Inc.:
Responsible Party: | Tesaro, Inc. |
ClinicalTrials.gov Identifier: | NCT02657889 |
Other Study ID Numbers: |
213363 3000-PN162-01-001 ( Other Identifier: Tesaro ) |
First Posted: | January 18, 2016 Key Record Dates |
Results First Posted: | February 11, 2020 |
Last Update Posted: | January 13, 2021 |
Last Verified: | December 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
PARP inhibitor PD-1 Niraparib |
Pembrolizumab Keynote TOPACIO |
Breast Neoplasms Ovarian Neoplasms Carcinoma, Ovarian Epithelial Triple Negative Breast Neoplasms Fallopian Tube Neoplasms Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Endocrine Gland Neoplasms Ovarian Diseases Adnexal Diseases Genital Neoplasms, Female Urogenital Neoplasms |
Endocrine System Diseases Gonadal Disorders Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Fallopian Tube Diseases Pembrolizumab Niraparib Antineoplastic Agents, Immunological Antineoplastic Agents Poly(ADP-ribose) Polymerase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |