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 Pembrolizumab, Niraparib
Eligible Participant

Platinum resistant, refractory or sensitive (platinum-ineligible) ovarian cancer with ≤ 5 prior therapies; no primary Pt-R/Pt-Rf

Patients Enrolled

62; median 3 prior therapies (1-5) (Phase I: 9, Phase II: 53); 63% w/ prior Bev

Therapy Setting


Study Design

Open-Label, Non-randomized


ORR, DCR, PFS, evaluated per RECIST


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


ORR: 18.3% (3CR, 8PR, n=60)
DCR: 65% (3CR, 8PR, 28SD, n=60)
PFS: 3.4 months

Exploratory analysis Pt status:
Pt-R (n=29): ORR: 21%
Pt-Rf (n=16): ORR: 13%
Results based on HRD status from figure 2B: 3CR, 12PR (4uPR)
tBRCA MUT (n=8): ORR: 37.5% (1CR, 2PR)
HRD+ (excl. tBRCA MUT, n=8): ORR: 25% (2PR)
HRD- (n=17): ORR: 41.2% (1CR, 6PR)
HRD unk (n=6): ORR: 33.3% (1CR, 1PR)
w/ prior Bev (n=37): ORR: 18.9%
w/o prior Bev (n=23): ORR: 17.4%

5 of 8 patients with long-term response (>6 months) were Pt-R/Pt-Rf and BRCA WT

Clinically Significant Adverse Events

Serious AE: none
Grade 3-4 AE: anemia (21%)


Promising activity of non-chemotherapy combination 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)

Konstantinopoulos PA et al. Single-Arm Phases 1 and 2 Trial of Niraparib in Combination With Pembrolizumab in Patients With Recurrent Platinum-Resistant Ovarian Carcinoma. JAMA Oncol (2019) 5(8):1141-1149

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