VVD-130037 + paclitaxel

VVD-130037 + paclitaxel is a combination therapy evaluated for advanced metastatic or unresectable solid tumors in ongoing Phase 1 trials. VVD-130037 is an orally administered, covalent, allosteric activator of Kelch-like ECH-associated protein 1 (KEAP1) that enhances KEAP1–CUL3 E3 ligase–mediated ubiquitination and degradation of nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor commonly upregulated in chemoresistant cancers. The mechanistic rationale is to counteract oncogenic NRF2 signaling, which drives resistance to standard chemotherapies, including taxanes. Paclitaxel is a classic taxane antineoplastic agent that stabilizes microtubules to induce mitotic arrest and apoptosis. The two drugs are being used in combination to test for safety, tolerability, pharmacokinetics, and synergistic antitumor activity in dose-escalation and dose-expansion trial arms. The developer of VVD-130037 is Vividion Therapeutics; this program is at first-in-human stage and not currently approved.