| Trial ID # | NCT01891344; ARIEL2 |
| Phase | II |
| Drug Class | DNA Damage Repair Pathway Inhibitors: PARP |
| Drug Name | Rucaparib |
| Alternate Drug Names | AG-014699, PF 01367338, CO-338, Rubraca |
| Drugs in Trial | Rucaparib |
| Eligible Participant | Recurrent high grade ovarian cancer |
| Patients Enrolled | 491 |
| Therapy Setting | Recurrence |
| Study Design | Open-Label, Non-randomized |
| Endpoints | ORR, PFS, evaluated per RECIST |
| Biomarkers | Exploratory: BRCA1/2; LOH (by FoundationFocus CDx BRCA LOH) |
| Efficacy | BRCA MUT (n=138) vs BRCA WT LOH high (n=156) vs BRCA WT LOH low (n=168): Pt-S vs Pt-R/Pt-Rf: 1-2 prior therapies, BRCA MUT (n=31) vs BRCA WT LOH high (n=57) vs BRCA WT LOH low (n=74): ≥3 prior therapies, BRCA MUT (n=107) vs BRCA WT LOH high (n=99) vs BRCA WT LOH low (n=94): Pt-S, BRCA MUT (n=74) vs BRCA WT LOH high (n=83) vs BRCA WT LOH low (n=112): Pt-R/Pt-Rf, BRCA MUT (n=64) vs BRCA WT LOH high (n=73) vs BRCA WT LOH low (n=56): |
| Clinically Significant Adverse Events | Serious AE: none |
| Conclusion | Administration of rucaparib as active treatment should be considered in earlier lines of therapy before the emergence of platinum resistance. RAD51C/D mutation and high-level BRCA1 promotor methylation predict response to rucaparib, similar to BRCA1/2 mutations, but LOH high is only predictive of response in platinum-sensitive patients |
| Reference | Swisher EM et al. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2). Nat Commun (2021) 12(1):2487 |