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DTRMWXHS-12 + everolimus + pomalidomide is an investigational, all-oral combination regimen for relapsed/refractory lymphomas, including chronic lymphocytic leukemia (CLL), B-cell non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma. The triplet therapy consists of: - DTRMWXHS-12 (also known as DTRM-12): a novel oral small molecule inhibitor of Bruton tyrosine kinase (BTK), which blocks B-cell receptor (BCR) signaling essential for malignant B-cell survival. - Everolimus: an oral small molecule inhibitor of the mammalian target of rapamycin (mTOR), a kinase that regulates cell proliferation, growth, and survival. - Pomalidomide: an oral immunomodulatory agent (IMiD) that modulates the immune microenvironment and exerts direct anti-tumor effects. This combination (also referred to as DTRM-555) aims to leverage synthetic lethality by inhibiting multiple signaling pathways critical for B-cell malignancy survival and resistance: BTK inhibition impairs BCR signaling, mTOR inhibition disrupts cellular proliferation cues, and immunomodulation via pomalidomide enhances anti-tumor immunity. In phase I studies, this regimen exhibited manageable toxicities and clinical activity in heavily pre-treated patients with relapsed/refractory B-cell lymphomas.
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