Part 1: AVANOVA1 - A Phase I Study to Evaluate the Safety and Tolerability of Bevacizumab-niraparib Combination Therapy and Determine the Recommended Phase 2 Dose (RP2D) in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer Part 2: AVANOVA2 - A Two-arm, Open-label, Phase II Randomized Study to Evaluate the Efficacy of Niraparib Versus Niraparib-bevacizumab Combination in Women With Platinum-sensitive Epithelial Ovarian, Fallopian Tube, or Peritoneal Cancer.

Trial ID # NCT02354131; AVANOVA
Phase II
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Niraparib
Alternate Drug Names MK4827, Zejula
Drugs in Trial Bevacizumab, Niraparib
Eligible Participant

Platinum-sensitive ovarian cancer, no prior PARP inhibitor

Patients Enrolled

109 (Phase I: 12; Phase II: Nir: 49, median 1 prior therapy; Nir+Bev: 48, median 2 prior therapies)

Therapy Setting

Recurrence

Study Design

Open-Label, Randomized

Endpoints

ORR, DCR, PFS, RP2D, evaluated per RECIST

Biomarkers

Exploratory: HRD, gBRCA, CFI, prior bevacizumab

Efficacy

AVANOVA1:
RP2D: Bev 15mg/kg IV Q3W and Nir 300mg QD

AVANOVA2:
Nir+Bev vs Nir:

ORR: 62 (7CR, 22PR, n=47) vs 30% (5CR, 8PR, n=44) (p=0.003)
DCR: 79 vs 53% (p=0.008)
PFS: 11.9 vs 5.5 months, HR: 0.35 (0.21 to 0.57, p<0.0001)

Exploratory subgroup analyses: HRD-status, gBRCA-status, CFI, prior avastin:
Nir+Bev vs Nir:

HRD-negative: PFS: 11.3 (n=20) vs 4.2 (n=19) months, HR: 0.40 (0.19-0.85, p=0.0129)
HRD-positive: PFS: 11.9 (n=28) vs 6.1 (n=30) months, HR: 0.38 (0.20-0.72, p=0.019)
non-gBRCA MUT: PFS: 11.3 (n=33) vs 4.2 (n=31) months, HR: 0.32 (0.17-0.58, p=0.0001)
gBRCA MUT: PFS: 14.4 (n=15) vs 9.0 (n=18) months, HR: 0.49 (0.21-1.15, p=0.0947)
non-gBRCA MUT, HRD-positive: PFS: 11.9 (n=13) vs 4.1 (n=12) months, HR: 0.19 (0.06-0.59)
CFI 6-12 months: PFS: 11.3 (n=20) vs 2.2 (n=17) months, HR: 0.29 (0.14-0.62, p=0.0006)
CFI >12 months: PFS: 13.1 (n=28) vs 6.1 (n=32) months, HR: 0.42; (0.20-0.80, p=0.0062)
No prior bevacizumab: PFS: 14.4 (n=38) vs 6.0 (n=35) months, HR: 0.39 (0.22-0.68)
Prior bevacizumab: PFS: 5.9 (n=10) vs 3.1 (n=13) months, HR: 0.51 (0.21-1.26)

Clinically Significant Adverse Events

Nir+Bev vs Nir:
Dose Limiting Toxicities: thrombocytopenia
Serious AE: none
Grade 3-4 AE: overall (65 vs 45%), hypertension (21 vs 0%)

Conclusion

Promising activity of non-chemotherapy

Reference

Mirza MS et al. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24): a randomised, phase 2, superiority trial. Lancet Oncol (2019) Aug 29
https://www.ncbi.nlm.nih.gov/pubmed/31474354

Mirza MR et al. A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24. Cancer Chemother Pharmacol (2019) Aug 2
https://www.ncbi.nlm.nih.gov/pubmed/31375879