Phase 2b HRX215 (darizmetinib) MKK4 inhibitor to accelerate liver regeneration after PVE.

This Phase 2b, randomized, placebo-controlled study at Mayo Clinic tests whether HRX215 (darizmetinib)—an oral small-molecule inhibitor of MKK4 (MAP2K4)—can increase future liver remnant growth after portal vein embolization (PVE) in patients with resectable colorectal liver metastases who are planning hepatectomy. Participants start HRX215 (or placebo) around the PVE procedure and continue twice daily dosing for ~4 weeks, then proceed to scheduled liver resection if appropriate; imaging and blood sampling track regeneration and safety, and optional tumor/liver tissue may be collected at surgery. The scientific angle is “regenerative pharmacology” in a peri-procedural window: rather than directly shrinking metastases, Mayo Clinic is testing whether transient MKK4 blockade can safely speed hypertrophy of the remnant liver and reduce post-hepatectomy liver failure risk, potentially converting more patients to curative-intent surgery. Today’s care for borderline/insufficient future liver remnant is PVE (or ALPPS in select cases) to induce hypertrophy, plus modern systemic therapy (FOLFOX/FOLFIRI ± bevacizumab; EGFR antibodies for RAS wild-type left-sided tumors) with liver-directed approaches when feasible, followed by hepatectomy when the remnant is adequate.