1143PD - Dose-finding combination study of niraparib and pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or recurrent p...

Date 11 September 2017
Event ESMO 2017 Congress
Session Immunotherapy of cancer
Topics Anticancer Agents
Cancers in Adolescents and Young Adults (AYA)
Ovarian Cancer
Breast Cancer
Gynaecological Malignancies
Biological Therapy
Presenter Panagiotis Konstantinopoulos
Citation Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376
Authors P.A. Konstantinopoulos1, J.C. Sachdev2, L. Schwartzberg3, U.A. Matulonis4, P. Sun5, J.Y. Wang5, W. Guo6, D. Bobilev7, G. Aktan8, V. Karantza9, B. Dezube7, S. Vinayak10
  • 1Gynecologic Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2Oncology, HonorHealth Research Institute, Scottsdale/US
  • 3Medical Oncology, The West Clinic, Memphis/US
  • 4Gynecologic Oncology, Dana Farber Cancer Institute, 2115 - Boston/US
  • 5Clinical Science, TESARO, Inc., Waltham/US
  • 6Biostatistics, TESARO, Inc., Waltham/US
  • 7Clinical Science, TESARO, Inc., 2451 - Waltham/US
  • 8Clinical Research, Merck & Co., Inc., Kenilworth/US
  • 9Oncology, Merck & Co., Inc., Kenilworth/US
  • 10Hematology And Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland/US



Platinum-resistant OC represents an unmet medical need with progression free survival (PFS) of 3.5 to 6 months. Niraparib, an oral PARP 1/2 inhibitor (PARPi), improved PFS in pts with recurrent OC following response to platinum (NEJM, 2016). Preclinical evidence suggests synergy between PARPis and PD-1 inhibitors in OC and TNBC. We report data from a phase 1 niraparib + pembrolizumab (pembro) combination study leading to recommended phase 2 dose (RP2D).


Primary objectives were to assess dose limiting toxicities (DLTs) in a 6 + 6 dose escalation design and determine RP2D. Eligible pts had metastatic TNBC treated with ≤4 prior lines of chemotherapy OR platinum-resistant recurrent OC treated with ≤5 prior lines of chemotherapy having responded with CR or PR for >6 months to 1st line platinum based chemotherapy.


The 14 pts (≥18 yrs) enrolled received pembro 200 mg IV on day 1 and niraparib 200 mg (dose level [DL] 1, n = 7; 2 TNBC, 5 OC) or 300 mg (DL2, n = 7; 3 TNBC, 4 OC) PO on days 1–21 of each 21-day cycle. In DL1, 1 pt had DLTs (neutropenia, anemia and thrombocytopenia) and discontinued niraparib but continued pembro. In DL2, 1 pt had DLT and 1 had DLT-equivalent (both thrombocytopenia); both resumed treatment with 200 mg niraparib and continued pembro. RP2D was determined as niraparib 200 mg PO daily + pembro 200 mg IV on day 1 of each 21-day cycle. Based on RECIST v1.1, 4/8 evaluable OC pts responded; the other 4 pts achieved SD (Table). 1/5 TNBC pts (BRCA wildtype) had SD for 10 cycles. BRCA & PD-L1 status will be presented.Table:


Best response OC N = 8Time to response$ Cycle (weeks)Time on study Cycle*
CR3 (9)11+
PR6 (18)9
PR6 (18)13+
PR3 (9)8
SD2 (6)3
SD3 (9)6
SD3 (9)5
SD3 (9)6

 + = ongoing


Assessed every 3 cycles


This study established a RP2D, and showed preliminary efficacy of niraparib and pembro combination for treatment of heavily pretreated TNBC or platinum-resistant OC. No significant overlapping toxicity was noted. A phase 2 study is currently enrolling. Supporting translational work funded by SU2C.

Clinical trial identification


Legal entity responsible for the study



TESARO, Inc. and Merck and Co.


P.A. Konstantinopoulos: Consulting/Advisory: Merck, Vertex. J.C. Sachdev: Consulting/Advisory: Celgene Honoraria: Celgene. L. Schwartzberg: Consulting/Advisory: Eisai, Teva, Amgen, Bristol-Myers Squibb, Helsinn Therapeutis, Tesaro, Spectrum Pharmaceuticals Speakers’ Bureau: Genentech, Bristol-Myers Squibb, Amgen. U.A. Matulonis: Consulting/Advisory: Merck KGaA, AstraZeneca, Immunogen, Tesaro, Genentech P. Sun, J.Y. Wang, W. Guo, B. Dezube: Employment: Tesaro Stock: Tesaro. D. Bobilev: Employment: Tesaro Stock: Tesaro Travel, Accommodations, Expenses: Tesaro G. Aktan: Employment: Merck Stock: Merck. V. Karantza: Employment: Merck Sharp & Dohme Stock: Merck Sharp & Dohme Patents, Royalties, IP: Merck Sharp & Dohme. S. Vinayak: Travel, Accommodations, Expenses: Tesaro.