KTX-1001 + mezigdomide + dexamethasone

KTX-1001 + mezigdomide + dexamethasone is an investigational, orally administered combination regimen in clinical development for the treatment of relapsed and refractory multiple myeloma, especially for high-risk genetic subtypes such as t(4;14) translocation. **KTX-1001** is a first-in-class, oral, selective inhibitor of NSD2/MMSET (also known as multiple myeloma SET domain-containing protein), targeting the epigenetic regulation driven by H3K36me2 methylation. **Mezigdomide** (also known as CC-92480) is an oral cereblon E3 ligase modulator (CELMoD) that recruits Ikaros and Aiolos (IKZF1, IKZF3) for proteasomal degradation via the CRL4Cereblon (CRBN) E3 ubiquitin ligase complex, resulting in antimyeloma activity via direct tumor cell apoptosis and immunomodulation. **Dexamethasone** is a synthetic glucocorticoid corticosteroid with anti-inflammatory and antineoplastic effects, commonly used as a backbone in myeloma regimens. Preclinical and early clinical evidence indicate synergy between KTX-1001 and mezigdomide, with dexamethasone enhancing antimyeloma activity. The combination is in phase 1 evaluation in relapsed/refractory multiple myeloma, with K36 Therapeutics managing clinical development in collaboration with Bristol Myers Squibb[1][2][5].