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.

Platinum sensitive ovarian cancer, no prior PARP inhibitor

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

Recurrence

Open-Label, Randomized

ORR, DCR, PFS, OS, RP2D, PFS2, TFST, evaluated per RECIST

Exploratory: HRD, gBRCA, CFI, prior bevacizumab

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: 12.5 vs 5.5 months, HR: 0.34 (0.21 to 0.54, p<0.0001)
TFST: 14.3 vs 7.2 months, HR: 0.45 (0.29-0.70, p=0.0004)
PFS2: 20.5 vs 15.7 months, HR: 0.56 (0.35-0.89, p=0.015)
OS: 29.4 vs 27.8 months, HR: 0.75 (0.44-1.29, p=0.30)

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

HRD-: PFS: 11.3 (n=20) vs 4.2 (n=19) months, HR: 0.40 (0.19-0.85, p=0.0129)
HRD+: 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+: 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 Bev: PFS: 14.4 (n=38) vs 6.0 (n=35) months, HR: 0.39 (0.22-0.68)
Prior Bev: PFS: 5.9 (n=10) vs 3.1 (n=13) months, HR: 0.51 (0.21-1.26)

Nir+Bev vs Nir:
Dose Limiting Toxicities: thrombocytopenia
Serious AE: none
Grade 3-4 AE: overall (65 vs 45%), hypertension (22.9 vs 0%)

Promising improvement of activity with niraparib+bevacizumab compared to niraparib alone

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) 20(10):1409-1419
https://www.ncbi.nlm.nih.gov/pubmed/31474354

Mirza MR et al. Final survival analysis of NSGO-AVANOVA2/ENGOT-OV24: Combination of niraparib and bevacizumab versus niraparib alone as treatment of recurrent platinum-sensitive ovarian cancer—A randomized controlled chemotherapy-free study. J Clin Oncol (2020) 38: (suppl; abstr 6012)
https://ascopubs.org/doi/abs/10.1200/JCO.2020.38.15_suppl.6012

Mirza MR et al. Poster
https://www.clearityfoundation.org/wp-content/uploads/2020/06/AVANOVA-ASCO-2020.pdf