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

Efficacy

AVANOVA1:
RP2D: Bev 15mg/kg IV every 21 days and Nir 300mg qd

AVANOVA2:
Nir+Bev vs Nir:

ORR: 60 vs 27% (p=0.001)
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:
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)
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)

Clinically Significant Adverse Events

Nir+Bev vs Nir:
Dose Limiting Toxicities: thrombocytopenia
Serious AE: none
Grade 3-4 AE: hypertension (26.5 vs 0%), neutropenia (12.2 vs 2.1%)

Conclusion

Promising activity of non-chemotherapy combination

Reference

Mirza MS et al. Combination of niraparib and bevacizumab in versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer. A randomized controlled chemotherapy-free study - NGSO- AVANOVA2/ENGOT-OV24. J Clin Oncol (2019) 37(suppl; abstr 5505)
https://meetinglibrary.asco.org/record/173447/abstract

Mirza MS et al. A phase I study of bevacizumab in combination withniraparib in patients with platinum-sensitive epithelial ovarian cancer:The ENGOT-OV24/AVANOVA1 trial. J Clin Oncol (2016) 34(suppl; abstr 5555)
http://abstract.asco.org/176/AbstView_176_167216.html