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 Anti-Cancer Agents & Biologic Therapy
Cancer in Adolescents
Ovarian Cancer
Breast Cancer
Cancer Immunology and Immunotherapy
Gynaecologic Malignancies
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.