RMC-9805-001

NCT06040541 📎

Regimen

Experimental
RMC-9805 (zoldonrasib) 150-1200 mg PO QD or 300-600 mg BID (dose-escalation); RP2D = 1200 mg total daily
Control
single-arm / no comparator (historical benchmark for 2L+ KRAS G12D PDAC = SoC chemo mOS 5-7 mo)

Population

Previously treated advanced solid tumors harboring KRAS G12D mutation (confirmed by tumor or ctDNA); PDAC subgroup at RP2D (1200 mg QD or 600 mg BID) n=42 enrolled ≥14 weeks prior to Sep 2024 cutoff. Global sites.

Key finding

First selective KRAS G12D(ON) inhibitor to show clinical antitumor activity in PDAC (the dominant KRAS variant in pancreatic cancer, ~40%). Manageable safety (grade 1-2 GI + rash, no grade 4-5 TRAEs). FDA Breakthrough Therapy Designation granted (NSCLC initially; PDAC development accelerating). Complements pan-KRAS RMC-6236 by offering a selective option and potential for combination strategies.