ICP-490 + dexamethasone

ICP-490 + dexamethasone is a combination therapy under investigation for the treatment of relapsed and/or refractory multiple myeloma and non-Hodgkin’s lymphoma. **ICP-490** is a novel, orally available small molecule that functions as a next-generation cereblon E3 ligase modulator (CELMoD), selectively and potently degrading IKZF1 (Ikaros) and IKZF3 (Aiolos) at sub-nanomolar concentrations. This leads to tumor cell death and immunomodulation, with reported activity superior to currently approved immunomodulatory drugs (IMiDs). It is designed to overcome IMiD resistance and lacks significant off-target degradation of proteins such as GSPT1, PLZF1, and SALL4. **Dexamethasone** is a synthetic glucocorticoid with anti-inflammatory and immunosuppressive properties, widely used in multiple myeloma regimens to induce apoptosis in malignant plasma cells and modulate immune response. Clinical studies show the combination is well tolerated, with preliminary efficacy demonstrated in multiple myeloma patients at ICP-490 doses ≥1.0 mg, resulting in deep degradation of primary biomarkers Aiolos (IKZF3) and Ikaros (IKZF1). ICP-490 is developed by InnoCare Pharma and is being evaluated in phase 1/2 trials for hematologic malignancies[1][2][3][4][5].