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 (TOPACIO)

Trial ID # NCT02657889; TOPACIO
Phase I/II
Drug Class DNA Damage Repair Pathway Inhibitors:PARP
Drug Name Niraparib
Alternate Drug Names MK4827, Zejula
Drugs in Trial Niraparib, Pembrolizumab
Eligible Participant

Recurrent Pt-R, Pt-Rf or Pt-S but-Pt ineligible; ≤ 5 prior therapies; no primary Pt-R/Pt-Rf

Patients Enrolled

62 (Phase I: 9, Phase II: 53)

Therapy Setting


Study Design

Open-Label, Non-randomized


ORR, DCR, DoR, evaluated per RECIST


Exploratory: BRCA1/2, HRD (myChoice HRD test, Myriad Genetics), PD-L1 protein


ORR: 25% (3CR, 12PR, n=60)
DCR: 62% (3CR, 12PR, 25SD, n=60)
DoR: 9.3 months

Exploratory analysis Pt status, HRD status:
Pt-R (n=30): ORR: 23%
Pt-Rf (n=17): ORR: 24%
Pt-R/Pt-Rf and BRCA WT (n=37): ORR: 24%
Pt-R/Pt-Rf and BRCA MUT (n=8): ORR: 25%
Pt-R/Pt-Rf and HRD pos (inc. BRCA MUT) (n=16): ORR: 25%
Pt-R/Pt-Rf and HRD neg (n=26): ORR: 27%

Clinically Significant Adverse Events

Serious AE: none
Grade 3-4 AE: anemia (19%)


Promising activity of non-chemotherapy combination in Pt-R/Pt-Rf patients independent of BRCA status, HRD status and PD-L1 expression


Konstantinopoulos PA et al. TOPACIO/Keynote-162 (NCT02657889): A phase 1/2 study of niraparib + pembrolizumab in patients (pts) with advanced triple-negative breast cancer or recurrent ovarian cancer (ROC)—Results from ROC cohort. J Clin Oncol (2018) 36 (suppl; abstr 106)