Article Text
Abstract
Introduction Low grade serous ovarian cancer (LGSOC) is a rare, clinically distinct cancer commonly driven by RAS/MAPK pathway alterations. Avutometinib ([A] oral RAF/MEK clamp) + defactinib ([D] oral FAK inhibitor) is being investigated in recurrent LGSOC. We report the primary analysis of A±D from RAMP 201.
Methods Patients with recurrent, measurable LGSOC after at least one line of platinum chemotherapy were enrolled. Patients were randomized to A (4.0mg BIW) monotherapy or A (3.2mg BIW) + D (200mg BID). A+D was selected for expansion. Subsequently a 1.6mg dose of A +D was evaluated. The primary endpoint is ORR per RECISTv1.1 by BICR.
Results At the 30June2024 visit cutoff, 115 patients were enrolled to A (3.2mg BIW) + D (200mg BID). Median age was 54 (range, 21-87) and patients had a median of 3 (range, 1-9) prior lines of therapy. Prior therapies included endocrine (86%), bevacizumab (51%), and MEK inhibitor (22%). Confirmed ORR of 31% was observed (44% KRAS mt; 17% KRAS wt); median DOR, 31.1mo and median PFS, 12.9mo. The most common non-laboratory treatment-related AEs (all grades, grade ≥3) were nausea (67.0%, 2.6%) and diarrhea (58.3%, 7.8%). The most common laboratory abnormality was increased blood creatinine phosphokinase (60.0%, 24.3%). Discontinuations due to AEs were infrequent (10%). Results from all cohorts will be presented.
Conclusion/Implications A+D was well tolerated allowing prolonged exposure to therapy. ORR and durable responses observed are clinically meaningful in this heavily pretreated population and support the potential of A+D as a new standard of care for recurrent LGSOC.