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vopimetostat + zoldonrasib
- Development stage
- Phase 2
- Lead developer
- REVOLUTION Medicines
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
Vopimetostat + zoldonrasib is an investigational, oral, chemotherapy-free combination therapy being evaluated for the treatment of MTAP-deleted, RAS-mutant cancers. The regimen combines vopimetostat (TNG462), an oral, once-daily, MTA-cooperative PRMT5 inhibitor developed by Tango Therapeutics, with zoldonrasib (RMC-9805), an oral, RAS(ON) G12D-selective covalent tri-complex inhibitor developed by Revolution Medicines. Vopimetostat selectively targets cancer cells harboring MTAP deletions by binding to the MTA-PRMT5 complex to induce synthetic lethality. Zoldonrasib binds to cyclophilin A to form a binary complex that selectively recognizes and inhibits the active, GTP-bound state of mutant KRAS G12D. This combination is being evaluated in a Phase 1/2 clinical trial (NCT06922591) for patients with metastatic pancreatic ductal adenocarcinoma (PDAC) or non-small cell lung cancer (NSCLC).
- Other names
- TNG-462 + RMC-9805TNG462 + RMC-9805vopimetostat and zoldonrasibvopimetostat/zoldonrasib
02
Targets
KRASG12D (Kirsten rat sarcoma viral oncogene homolog (KRAS) G12D mutant)MTAP (Methylthioadenosine phosphorylase)PPIA (Peptidyl-prolyl cis-trans isomerase A)PRMT5 (Protein arginine N-methyltransferase 5)
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