KRYSTAL-1-PANC

NCT03785249 📎

Regimen

Experimental
Adagrasib (MRTX849) 600 mg PO BID continuous
Control
single-arm / no comparator (historical 2L PDAC benchmark ORR <10%, mOS 5-7 mo)

Population

Previously treated unresectable/metastatic PDAC with KRAS G12C mutation (a rare variant, ~1-2% of PDAC); pancreatic cohort n=21 within the 64-pt non-NSCLC/non-CRC cohort of KRYSTAL-1 (Bekaii-Saab JCO 2023).

Key finding

First prospective cohort to show clinical activity of a selective KRAS G12C inhibitor in previously treated PDAC. ORR 33% in a disease where 2L historical ORR is single-digit. Manageable safety (mainly GI toxicity, no grade 4-5 TRAEs). Validated the biomarker-matched precision approach in PDAC for the G12C subset (a small slice of the KRAS-mutant PDAC population, but the first to be addressable).

Source: PMID 37099736

Timeline

    Guideline citations

    • NCCN PANCREATIC (p.149)