Phase 1/2 BLU-924 (SAR449336) pan-KRAS inhibitor in KRAS-mutant PDAC/NSCLC/CRC

This first-in-human, open-label Phase 1/2 trial tests BLU-924 (SAR449336), an oral pan-KRAS small-molecule inhibitor, as monotherapy and in combination therapy in people with metastatic, KRAS-mutant pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), or colorectal cancer (CRC). Sponsored by Blueprint Medicines, the study uses dose escalation to define safety/tolerability, pharmacokinetics, and a recommended dose for further evaluation, then moves into dose enrichment and indication-specific dose expansion cohorts to better estimate antitumor activity and pharmacodynamics. Eligibility focuses on patients whose PDAC/NSCLC/CRC has progressed after available standard therapies; in practice, this often means prior multi-agent chemotherapy (and, where appropriate, immunotherapy for subsets of NSCLC/CRC) with limited remaining targeted options for many KRAS variants. The key scientific/commercial angle is broad KRAS coverage (not limited to KRAS G12C), aiming to address a large unmet need across three high-incidence tumor types where KRAS mutations are common.