A Phase 2, Open-Label, Single-Arm Study to Evaluate the Safety and Efficacy of Niraparib in Patients With Advanced, Relapsed, High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer Who Have Received Three or Four Previous Chemotherapy Regimens (QUADRA)

Recurrent advanced high grade serous ovarian cancer with ≥ 3 prior therapies

463; median 4 prior therapies (3-16)

Recurrence

Open-Label, Non-randomized

CBR, ORR, DCR, DoR, OS, evaluated per RECIST

Exploratory: BRCA1/2, HRD (myChoice HRD test, Myriad Genetics)

Primary endpoint analysis: Pt-S, HRD+ (incl. BRCA MUT) with 3 or 4 prior therapies, no prior PARPi (n=47):
ORR: 28% (p=0.00053); DCR: 68%; DoR: 9.2 months; PFS: 5.5 months

Exploratory analysis Pt status and BRCA status (Modified Per Protocol Population: ≥3 prior therapies, no prior PARPi):
Pt-S, BRCA MUT (n=18): ORR: 39%; CBR: 56%
Pt-S, HRD+ (incl. BRCA MUT) (n=53): ORR: 26%; CBR: 40%
Pt-S, HRD+ (excl. BRCA MUT) (n=35): ORR: 20% (FDA approval data); CBR: 31% (Fig. 4A)
Pt-S, HRD- or unk (n=52): ORR: 4%; CBR: 19%
Pt-R or Pt-Rf, BRCA MUT (n=37): ORR: 27%; CBR: 32%
Pt-R or Pt-Rf, HRD+ (incl. BRCA MUT) (n=120): ORR: 10%; CBR: 20%
Pt-R or Pt-Rf, HRD+ (excl. BRCA MUT): CBR: 14% (Fig. 4A)
Pt-R or Pt-Rf, HRD- or unk (n=169): ORR: 3%; CBR: 11%

Serious AE: overall (43%), small intestinal obstruction (7%), thrombocytopenia (7%), vomiting (6%), 1 death due to gastric hemorrhage
Grade 3-4 AE: anemia (24%), thrombocytopenia (21%)

Some activity in late-line treatment setting

Moore KN et al. Niraparib monotherapy for late-line treatment of ovarian cancer (QUADRA): a multicentre, open-label, single-arm, phase 2 trial. Lancet (2019) 20(5):636-648
https://www.ncbi.nlm.nih.gov/pubmed/30948273

Niraparib FDA prescribing information, 4/2020
https://www.clearityfoundation.org/wp-content/uploads/2020/04/Niraparib-prescribing-info-04-2020.pdf