Clinical trial NCT02657889: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Tesaro, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2016-01-18
Enrollment: 122
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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)


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)

Primary outcomes:
measure: Phase 1: Number of Participants Reporting Dose-Limiting Toxicities (DLTs)
timeFrame: During Cycle 1, ie, during the first 21 days of treatment
measure: Phase 2: Objective Response Rate (ORR) as Measured by Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
timeFrame: Up to 40 weeks
Secondary outcomes:
measure: Phase 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to a maximum of 22 months
measure: Phase 2: Number of Participants With TEAEs
timeFrame: Up to a maximum of 54 months
measure: Phase 2: Overall Response Rate (ORR) as Measured by Immune-related RECIST (irRECIST)
timeFrame: Up to a maximum of 54 months
measure: Phase 2: Duration of Response (DOR) as Measured by RECIST v1.1
timeFrame: Up to a maximum of 54 months
measure: Phase 2: DOR as Measured by irRECIST
timeFrame: Up to a maximum of 54 months
measure: Phase 2: Disease Control Rate (DCR) as Measured by RECIST v1.1
timeFrame: Up to 40 weeks
measure: Phase 2: DCR as Measured by irRECIST
timeFrame: Up to a maximum of 54 months
measure: Phase 2: Progression Free Survival (PFS) as Measured by RECIST v1.1
timeFrame: Up to a maximum of 54 months
measure: Phase 2: PFS as Measured by irRECIST
timeFrame: Up to a maximum of 54 months
measure: Phase 2: Overall Survival (OS)
timeFrame: Up to a maximum of 54 months
measure: Phase 1: Area Under the Plasma Concentration-time Curve From Time 0 (Predose) to 24 Hours Post Dose (AUC [0-24]) of Niraparib
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)
measure: Phase 1: AUC (0-24) of Major Metabolite of Niraparib (M1)
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)
measure: Phase 1: Minimum Observed Plasma Concentration (Cmin) and Maximum Observed Plasma Concentration (Cmax) of Niraparib
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)
measure: Phase 1: Cmin and Cmax of Major Metabolite of Niraparib (M1)
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)
measure: Phase 1: Apparent Oral Clearance (CL/F) of Niraparib
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)
measure: Phase 1: Apparent Oral Clearance (CL/F) of Major Metabolite of Niraparib (M1)
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)
measure: Phase 1: Volume of Distribution (Vz/F) of Niraparib
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)
measure: Phase 1: Volume of Distribution (Vz/F) of Major Metabolite of Niraparib (M1)
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 1 Day 1 (each cycle of 21 days)
measure: Phase 1: AUC at Steady State (AUC,ss) of Niraparib
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days)
measure: Phase 1: AUC,ss of Major Metabolite of Niraparib (M1)
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days)
measure: Phase 1: Minimum Observed Plasma Concentration at Steady State (Cmin,ss) and Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Niraparib
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days)
measure: Phase 1: Cmin,ss and Cmax,ss of Major Metabolite of Niraparib (M1)
timeFrame: Pre-dose and 1, 2, 4, 6, 8, 24 Hours post-dose on Cycle 2 Day 1(each cycle of 21 days)
measure: Phase 2: Plasma Concentrations of Niraparib
timeFrame: Pre-dose and 2 Hours post-dose on Cycle 1 Day 1; Pre-dose and 2 Hours post-dose on Cycle 2 Day 1(each cycle of 21 days)
measure: Phase 2: Plasma Concentrations of Major Metabolite of Niraparib (M1)
timeFrame: Pre-dose and 2 Hours post-dose on Cycle 1 Day 1; Pre-dose and 2 Hours post-dose on Cycle 2 Day 1 (each cycle of 21 days)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: GSK Investigational Site
state: Alabama
city: Phoenix
country: United States
facility: GSK Investigational Site
state: Arizona
city: Scottsdale
country: United States
facility: GSK Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: San Francisco
country: United States
facility: GSK Investigational Site
state: California
city: Stanford
country: United States
facility: GSK Investigational Site
state: California
city: Washington
country: United States
facility: GSK Investigational Site
state: District of Columbia
city: Deerfield Beach
country: United States
facility: GSK Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Orlando
country: United States
facility: GSK Investigational Site
state: Florida
city: Chicago
country: United States
facility: GSK Investigational Site
state: Illinois
city: Covington
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Boston
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Burlington
country: United States
facility: GSK Investigational Site
state: Massachusetts
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: Morristown
country: United States
facility: GSK Investigational Site
state: New Jersey
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Chapel Hill
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Germantown
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Charlottesville
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.