2519 - QUADRA: A phase 2, open-label, single-arm study to evaluate niraparib in patients (pts) with relapsed ovarian cancer (ROC) in 4th or later line of therapy: results from the tBRCAmut subset

Background

Therapeutic options in late line ROC offer limited efficacy, especially for pts who are considered platinum (plat) resistant (res) or refractory (ref). Pts whose cancers harbor BRCA mutations (BRCAmut) have been included in poly (ADP-ribose) polymerase inhibitor (PARPi) trials and derived modest benefit from treatment (ORR ≈25% for plat-res and 0-14% for plat-ref pts). QUADRA evaluated niraparib monotherapy in ROC pts regardless of their plat and biomarker status.

Methods

Eligible pts received treatment with single agent niraparib in 4^th or later line of therapy. Pts were evaluated for BRCAmut and HRD status (MyChoice HRD Test). Pts received niraparib 300 mg once daily until progression; treatment emergent adverse events (AEs) were managed with dose reduction to 200 or 100 mg. The primary endpoint was ORR per RECIST v1.1.

Results

463 pts were treated. Median age was 65 years (range: 29-91). 162 pts were plat ref (defined as progression within 28 days of the last dose of plat); 152 plat res (defined as less than 6 months between last dose of plat and subsequent progression); 118 plat sensitive; 31 unknown. Results in HRD+ pts have been presented at a prior congress. We focus here on the tBRCAmut (both germline and somatic) PARPi-naïve subgroup. ORR for 4^th line or later, PARPi-naïve tBRCAmut pts (n = 55) was 31% (95% CI: 19-45), including 18 plat-sensitive pts (ORR 39%), 21 plat-res pts (ORR 33%), and 16 plat-ref pts (ORR 19%). The combined ORR in the plat-res and -ref pts (n = 37) was 27%. The median DOR among all tBRCAmut pts was 9.2 months, with an estimated 43% of responding pts maintaining their response at 24 months. In the entire study cohort, 197 pts (42.5%) experienced a serious AE (SAE) and 91 pts (19.7%) a treatment-related SAE. The most frequent treatment-emergent SAEs were gastrointestinal disorders (19.9%), thrombocytopenia (8.4%), small intestinal obstruction (6.6%), and vomiting (5.1%).

Conclusions

Niraparib demonstrated meaningful and durable responses among the difficult-to-treat patient population, including platinum resistant and refractory tBRCAmut patients.

Clinical trial identification

NCT02354586.

Legal entity responsible for the study

Tesaro, Inc.

Funding

Tesaro, Inc.

Editorial Acknowledgement

Writing and editorial support, funded by Tesaro, Inc. (Waltham, MA, USA) and coordinated by Ted Paunescu, PhD of TESARO, Inc., was provided by Nicole Renner, PhD and Dena McWain of Ashfield Healthcare Communications (Middletown, CT, USA).

Disclosure

K.N. Moore: Honorarium and served on advisory boards: Tesaro, Genentech Roche, Clovis, Astra Zeneca (for agents not involved in the SOLO-a Study), Immunogen, VBL Therapeutics, Janssen. M. Geller: Advisory Role, Speakers' bureau & Research funding: Tesaro Inc. D.S. Miller: Advisory role: Eisai, ImmunoGen, Tesaro, Clovis Oncology, Genentech, AstraZeneca, Guardant Health, Alexion. Speakers' bureau: Genentech, Clovis; Research funding: Tracon, AstraZeneca, Tesaro, Janssen, Aeterna Zentaris, Genentech, Pfizer, Aprea AB, ImmunoGen, Takeda, Xenetic Biosciences. N.G. Cloven: Employment: Texas Oncology. G.F. Fleming: Research funding: Corcept Therapeutics. P. DiSilvestro: Advisory role: Tesaro, AstraZeneca; Research funding: AstraZeneca, Tesaro, Abbvie, Genentech, Roche, Janssen. A. Oza: Steering Committees for PARPi trials: Tesaro, Clovis, AstraZeneca; Honoraria: Intas Pharma. M. Cristea: Research funding: Trovagene. J.S. Berek: Advisory role: Atara Biotherapeutics; Research funding: Tesaro. J.K. Chan: Advisory role: Roche/Genentech, AstraZeneca, Janssen Oncology, Clovis, Mateon, Biodesix, Tesaro; Spearkers' bureau and Honoraria: Roche/Genentech, AstraZeneca, Clovis, Tesaro. Y. Li, K. Luptakova, R. Clark: Employment and stock and other ownership interests: Tesaro Inc. U.A. Matulonis: Advisory role: Merck KGaA, AstraZeneca, Immunogen, Tesaro, Genentech. B.J. Monk: Advisory role: GSK, Merck, Tesaro, Roche/Genentech, AstraZeneca,Gradalis, Advaxis, Verastem, Cerulean Pharma, Amgen, Vermillion, Immunogen, Bayer, NuCana BioMed, Insys Therapeutics, Clovis, Oxigene, Pfizer, Mateon, Precision, Perthera, Biodesix, Abbvie, Myriad, Incyte; Spearkers' bureau: Roche/Genentech, AstraZeneca, Janssen, Clovis, Tesaro; Honoraria: GSK, Merck, Tesaro, Roche/Genentech, AstraZeneca, Gradalis, Advaxis, Veraste, Cerulean, Amgen Vermillion, Bayer, NuCana BioMed, Insys Therapeutics, Clovis, Oxigene, Pfizer Mateon, Precision, Perthera, Biodesix, Abbvie, Myriad, Incyte, Janssen. All other authors have declared no conflicts of interest.