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Immunotherapy of cancer

2990 - Dose-finding combination study of niraparib and pembrolizumab in patients (pts) with metastatic triple-negative breast cancer (TNBC) or recurrent platinum-resistant epithelial ovarian cancer (OC) (TOPACIO/Keynote-162)

Date

11 Sep 2017

Session

Immunotherapy of cancer

Presenters

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

Author affiliations

  • 1 Gynecologic Oncology, Dana-Farber Cancer Institute, 02215 - Boston/US
  • 2 Oncology, HonorHealth Research Institute, Scottsdale/US
  • 3 Medical Oncology, The West Clinic, Memphis/US
  • 4 Gynecologic Oncology, Dana Farber Cancer Institute, 2115 - Boston/US
  • 5 Clinical Science, TESARO, Inc., Waltham/US
  • 6 Biostatistics, TESARO, Inc., Waltham/US
  • 7 Clinical Science, TESARO, Inc., 2451 - Waltham/US
  • 8 Clinical Research, Merck & Co., Inc., Kenilworth/US
  • 9 Oncology, Merck & Co., Inc., Kenilworth/US
  • 10 Hematology And Oncology, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland/US
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Resources

Abstract 2990

Background

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).

Methods

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.

Results

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:

1143PD

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

Conclusions

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

NCT02657889

Legal entity responsible for the study

TESARO, Inc.

Funding

TESARO, Inc. and Merck and Co.

Disclosure

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.

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