A Phase 3 Randomized Double-blind Trial of Maintenance With Niraparib Versus Placebo in Patients With Platinum Sensitive Ovarian Cancer (NOVA)

Trial ID # NCT01847274; NOVA
Phase III
Drug Class DNA Damage Repair Pathway Inhibitors:PARP
Drug Name Niraparib
Alternate Drug Names MK4827, Zejula
Drugs in Trial Niraparib
Eligible Participant

Platinum-sensitive recurrence and CR or PR in most recent Pt-based therapy, ≥ 2 Pt-based regimens

Patients Enrolled

553

Therapy Setting

Maintenance

Study Design

Double Blind, Randomized

Endpoints

PFS, evaluated per RECIST

Biomarkers

Exploratory: BRCA1/2, HRD status (myChoice HRD test, Myriad Genetics), 43-gene NGS assay (Myriad Genetics)

Efficacy

Nir maint vs Placebo (BICR):

non-gBRCA MUT (n=350):
PFS: 9.3 vs 3.9 months, HR: 0.45 (0.34-0.61, p<0.001)
gBRCA MUT (n=203):
PFS: 21.0 vs 5.5 months, HR: 0.27 (0.17-0.41, p<0.001)
non-gBRCA MUT, HRD-pos (n=162):
PFS: 12.9 vs 3.8 months, HR: 0.38 (0.24-0.59, p<0.001)

Exploratory analysis HRD status, sBRCA status, all non-gBRCA MUT:
HRD-pos, sBRCA WT (n=115): PFS: 9.3 vs 3.7 months, HR: 0.38 (0.23-0.63, p<0.001)
HRD-pos, sBRCA MUT (n=47): PFS: 20.9 vs 11.0 months, HR: 0.27 (0.08-0.90, p=0.02)
HRD-neg (n=134): PFS: 6.9 vs 3.8 months, HR: 0.58 (0.36-0.92, p=0.02)

Clinically Significant Adverse Events

Nir vs Placebo:
Serious AE: 2 treatment-related deaths, 1 in each arm
Grade 3-4 AE: any (74.1 vs 22.9%), thrombocytopenia (33.8 vs 0.6%), anemia (25.3 vs 0%), neutropenia (19.6 vs 1.7%), fatigue (8.2 vs 0.6%), hypertension (8.2 vs 2.2%)

Conclusion

Improved PFS for all patients with niraparib maintenance with most effect in BRCA MUT patients

Reference

Mirza MB et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. NEJM (2016) 375: 2154-2164
https://www.ncbi.nlm.nih.gov/pubmed/27717299