A Phase 3 Placebo-Controlled Study of Carboplatin/Paclitaxel With or Without Concurrent and Continuation Maintenance Veliparib (PARP Inhibitor) in Subjects With Previously Untreated Stages III or IV High-Grade Serous Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Trial ID # NCT02470585; VELIA
Phase III
Drug Class DNA Damage Repair Pathway Inhibitors: PARP
Drug Name Veliparib
Alternate Drug Names ABT-888
Drugs in Trial Carboplatin, Paclitaxel, Veliparib
Eligible Participant

Newly Diagnosed Stage III or IV, High-grade Serous, Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

Patients Enrolled

1140

Therapy Setting

First-line

Study Design

Double Blind, Randomized

Endpoints

PFS, evaluated per RECIST

Efficacy

CarboPt+Pac+Vel w/Vel maint vs CarboPt+Pac+Vel vs CarboPt+Pac:

All patients:
PFS: 23.5 vs 15.2 vs 17.3 months, HR: 0.68 (0.56-0.83, p<0.001), 1.07 (0.90-1.29)
BRCA MUT:
PFS: 34.7 vs 21.1 vs 22.0 months, HR: 0.44 (0.28-0.68, p<0.001), 1.22 (0.82-1.80)
HRD+ (incl. BRCA MUT):
PFS: 31.9 vs 18.1 vs 20.5 months, HR: 0.57 (0.43-0.76, p<0.001), 1.10 (0.86-1.41)

Exploratory analyses:
BRCA WT:
PFS: 18.2 vs 14.5 vs 15.1 months, HR: 0.80 (0.64-1.00)
HRD-:
PFS: 15.0 vs 12.9 vs 11.5 months, HR: 0.81 (0.60-1.09)

Clinically Significant Adverse Events

CarboPt+Pac+Vel w/Vel maint vs CarboPt+Pac+Vel vs CarboPt+Pac:
Serious AE: 1 AML vs 1 MDS vs none
Grade 3-4 AE: any (77 vs 88 vs 88%), neutropenia (49 vs 62 vs 58%), anemia (26 vs 41 vs 38%), thrombocytopenia (8 vs 31 vs 28%), leukopenia (9 vs 12 vs 18%)

Conclusion

Veliparib added to chemotherapy and continued as maintenance significantly extends PFS in all newly diagnosed patients, but shows most benefit in BRCA MUT patients

Reference

Coleman RF et al. Veliparib with First-Line Chemotherapy and as Maintenance Therapy in Ovarian Cancer. N Engl J Med (2019) 381(25):2403-2415
https://www.ncbi.nlm.nih.gov/pubmed/31562800