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 platinum-based therapy, ≥ 2 platinum-based regimens

Patients Enrolled

553

Therapy Setting

Maintenance

Study Design

Double Blind, Randomized

Endpoints

PFS, PFS2, 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)
PFS2: HR: 0.81 (0.62-1.05)
gBRCA MUT (n=203):
PFS: 21.0 vs 5.5 months, HR: 0.27 (0.17-0.41, p<0.001)
PFS2: HR: 0.67 (0.48-0.95)
HRD+ (excl. gBRCA MUT) (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, response after chemo:
HRD+ (excl. gBRCA MUT, excl. sBRCA MUT) (n=115): PFS: 9.3 vs 3.7 months, HR: 0.38 (0.23-0.63, p<0.001)
HRD+ (excl. gBRCA MUT, incl. sBRCA MUT) (n=47): PFS: 20.9 vs 11.0 months, HR: 0.27 (0.08-0.90, p=0.02)
HRD- (n=134): PFS: 6.9 vs 3.8 months, HR: 0.58 (0.36-0.92, p=0.02)
gBRCA MUT, CR after chemo: HR: 0.30 (0.16-0.55, p<0.0001)
gBRCA MUT, PR after chemo: HR: 0.26 (0.13-0.44, p<0.0001)
Non-gBRCA MUT, CR after chemo: HR: 0.58 (0.38-0.87, p=0.0082)
Non-gBRCA MUT, PR after chemo: HR: 0. 35 (0.23-0.53, p<0.0001)

Clinically Significant Adverse Events

Nir vs Placebo:
Serious AE: MDS/AML: (3.5 vs 1.7%), 6.6% of gBRCA MUT patients in Niraparib 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 greatest activity in BRCA MUT patients; the benefit of niraparib maintenance therapy extends beyond first progression

Reference

Mirza MB et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N Engl J Med (2016) 375(22): 2154-2164
https://www.ncbi.nlm.nih.gov/pubmed/27717299

Del Campo JM et al. Niraparib Maintenance Therapy in Patients With Recurrent Ovarian Cancer After a Partial Response to the Last Platinum-Based Chemotherapy in the ENGOT-OV16/NOVA Trial. J Clin Oncol (2019) 37(32):2968-2973
https://pubmed.ncbi.nlm.nih.gov/31173551/

Matulonis U et al. Long-term safety and secondary efficacy endpoints in the ENGOT-OV16/NOVA phase III trial of niraparib in recurrent ovarian cancer. SGO (2021) abstract 11139
https://www.clearityfoundation.org/wp-content/uploads/2021/03/SGO-11139-NOVA-Matulonis.pdf

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