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

NCT02657889 | Completed Phase 1 Results

• 2 other identifiers: 2133633000-PN162-01-001
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 30

Brief Summary

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)

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Phase 1: Number of Participants Reporting Dose-Limiting Toxicities (DLTs)

  DLTs are defined as: Any treatment-related Grade \>=3 non-hematologic clinical (non-laboratory) adverse event (AE); Any treatment-related Grade 3 or Grade 4 non-hematologic laboratory (lab) abnormality if Medical intervention is required to treat the participant 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 non-hematologic AE leading to \<80 percent (%) of an intended dose being administered.

  During Cycle 1, ie, during the first 21 days of treatment

• Phase 2: Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1

  ORR is defined as the percentage of participants with a confirmed best overall response of Complete Response (CR) or Partial Response (PR), RECIST v1.1 for target lesions as assessed by the Investigator. CR is defined as disappearance of all target lesions, Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis; PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the Baseline sum diameters.

  Up to 40 weeks

Secondary Outcomes (24)

• Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  Up to a maximum of 22 months

• Phase 2: Number of Participants With TEAEs

  Up to a maximum of 54 months

• Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST)

  Up to a maximum of 54 months

• Phase 2: Duration of Response (DOR) as Measured by RECIST v1.1

  Up to a maximum of 54 months

• Phase 2: DOR as Measured by irRECIST

  Up to a maximum of 54 months

Study Arms (1)

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

Drug: niraparib; Biological: pembrolizumab

Interventions

niraparib DRUG

niraparib plus pembrolizumab

pembrolizumab BIOLOGICAL

niraparib plus pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Tesaro, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (30)

GSK Investigational Site

Birmingham, Alabama, 35249, United States

Location

GSK Investigational Site

Phoenix, Arizona, 85054, United States

Location

GSK Investigational Site

Scottsdale, Arizona, 85258, United States

Location

GSK Investigational Site

Los Angeles, California, 90048, United States

Location

GSK Investigational Site

San Francisco, California, 94115, United States

Location

GSK Investigational Site

Stanford, California, 94305, United States

Location

GSK Investigational Site

Washington D.C., District of Columbia, 20007, United States

Location

GSK Investigational Site

Deerfield Beach, Florida, 33442, United States

Location

GSK Investigational Site

Jacksonville, Florida, 32224, United States

Location

GSK Investigational Site

Miami, Florida, 33136, United States

Location

GSK Investigational Site

Orlando, Florida, 32804, United States

Location

GSK Investigational Site

Chicago, Illinois, 60637, United States

Location

GSK Investigational Site

Covington, Louisiana, 70433, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02111, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02114, United States

Location

GSK Investigational Site

Boston, Massachusetts, 02115, United States

Location

GSK Investigational Site

Burlington, Massachusetts, 01805, United States

Location

GSK Investigational Site

Detroit, Michigan, 48201, United States

Location

GSK Investigational Site

Rochester, Minnesota, 55905, United States

Location

GSK Investigational Site

Morristown, New Jersey, 07962, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Chapel Hill, North Carolina, 27514, United States

Location

GSK Investigational Site

Charlotte, North Carolina, 28204, United States

Location

GSK Investigational Site

Cleveland, Ohio, 44106, United States

Location

GSK Investigational Site

Oklahoma City, Oklahoma, 73104, United States

Location

GSK Investigational Site

Germantown, Tennessee, 38138, United States

Location

GSK Investigational Site

Nashville, Tennessee, 37203, United States

Location

GSK Investigational Site

San Antonio, Texas, 78229, United States

Location

GSK Investigational Site

Charlottesville, Virginia, 22903, United States

Location

GSK Investigational Site

Seattle, Washington, 98109, United States

Location

Related Publications (3)

• Farkkila A, Gulhan DC, Casado J, Jacobson CA, Nguyen H, Kochupurakkal B, Maliga Z, Yapp C, Chen YA, Schapiro D, Zhou Y, Graham JR, Dezube BJ, Munster P, Santagata S, Garcia E, Rodig S, Lako A, Chowdhury D, Shapiro GI, Matulonis UA, Park PJ, Hautaniemi S, Sorger PK, Swisher EM, D'Andrea AD, Konstantinopoulos PA. Immunogenomic profiling determines responses to combined PARP and PD-1 inhibition in ovarian cancer. Nat Commun. 2020 Mar 19;11(1):1459. doi: 10.1038/s41467-020-15315-8.

  PMID: 32193378 DERIVED

• Konstantinopoulos PA, Waggoner S, Vidal GA, Mita M, Moroney JW, Holloway R, Van Le L, Sachdev JC, Chapman-Davis E, Colon-Otero G, Penson RT, Matulonis UA, Kim YB, Moore KN, Swisher EM, Farkkila A, D'Andrea A, Stringer-Reasor E, Wang J, Buerstatte N, Arora S, Graham JR, Bobilev D, Dezube BJ, Munster P. Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma. JAMA Oncol. 2019 Aug 1;5(8):1141-1149. doi: 10.1001/jamaoncol.2019.1048.

  PMID: 31194228 DERIVED

• Vinayak S, Tolaney SM, Schwartzberg L, Mita M, McCann G, Tan AR, Wahner-Hendrickson AE, Forero A, Anders C, Wulf GM, Dillon P, Lynce F, Zarwan C, Erban JK, Zhou Y, Buerstatte N, Graham JR, Arora S, Dezube BJ, Telli ML. Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer. JAMA Oncol. 2019 Aug 1;5(8):1132-1140. doi: 10.1001/jamaoncol.2019.1029.

  PMID: 31194225 DERIVED

MeSH Terms

Conditions

Neoplasms; Triple Negative Breast Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Fallopian Tube Neoplasms

Interventions

niraparib; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Fallopian Tube Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 18, 2016
• Study Start: April 15, 2016
• Primary Completion: May 14, 2018
• Study Completion: September 17, 2021
• Last Updated: December 1, 2022
• Results First Posted: February 11, 2020

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (30)