Investigational Drug
TNG462
TrialFetch AI Analysis
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Overview
Vopimetostat (TNG462) is an investigational oral cancer drug being studied alone and with other treatments in people whose solid tumors have an MTAP deletion. Human results are available from ongoing phase 1/2 studies, but they are preliminary and have not established whether the drug improves survival. (ir.tangotx.com)
Mechanism of action
TNG462 inhibits PRMT5, an enzyme involved in protein methylation. Loss of MTAP causes methylthioadenosine (MTA) to accumulate; TNG462 is designed to cooperate with MTA in inhibiting PRMT5, making MTAP-deleted cancer cells more susceptible than cells with intact MTAP. This selectivity has been demonstrated in preclinical research. (pubmed.ncbi.nlm.nih.gov)
Efficacy
In a company-reported analysis of single-agent treatment, 94 evaluable patients with various MTAP-deleted cancers treated at active doses had a 27% objective response rate and median progression-free survival of 6.4 months. A subgroup with second-line pancreatic cancer had a 25% response rate and median progression-free survival of 7.2 months. (ir.tangotx.com)
For combination treatment, a June 2026 company update reported responses in 11 of 12 evaluable patients with pancreatic cancer receiving TNG462 plus daraxonrasib (92%; nine responses confirmed), and 14 of 27 receiving TNG462 plus zoldonrasib (52%; ten confirmed). These are small, early, non-randomized groups; the response rates do not establish how much benefit TNG462 adds to either partner drug. (ir.tangotx.com)
Safety
In the single-agent analysis, the most common treatment-related adverse events included nausea (26%), anemia (20%), fatigue (19%), altered taste (19%) and low platelet counts (13%). Grade 3 anemia occurred in 13%; no treatment-related grade 4 or 5 events were reported. In the early combination analysis, common treatment-related events included rash, mouth inflammation and diarrhea with daraxonrasib, and nausea and vomiting with zoldonrasib. Three dose-limiting toxicities occurred in two patients in the higher-dose daraxonrasib combination group. Longer follow-up is needed to characterize safety. (ir.tangotx.com)
Further reading
- Peer-reviewed study of TNG462’s discovery and preclinical mechanism
- Phase 1/2 single-agent results reported by the study sponsor
- Initial combination results reported by the study sponsor
Last updated: Sep 2026
Active trials using TNG462
Found 3 active trials using this drug:
TrialFetch AI summary: Adults with previously treated advanced pancreatic ductal adenocarcinoma or NSCLC harboring MTAP loss and a RAS mutation receive oral vopimetostat (TNG462), an MTAP-selective PRMT5 inhibitor, plus either daraxonrasib (RMC-6236), a multi-variant RAS inhibitor, or zoldonrasib (RMC-9805), a KRAS G12D inhibitor. Prior RAS-targeted therapy, PRMT5 inhibitors, or MAT2A inhibitors are excluded.
ClinicalTrials.gov ID: NCT06922591
TrialFetch AI summary: Adults with advanced or metastatic MTAP-homozygously deleted solid tumors that have progressed after prior treatment and have no effective standard therapy receive oral S095035, a MAT2A inhibitor, alone or with TNG462, a PRMT5 inhibitor. Eligible tumors include NSCLC, biliary tract, pancreatic, gastroesophageal, and IDH-wild-type glioblastoma.
ClinicalTrials.gov ID: NCT06188702
TrialFetch AI summary: Adults with previously treated, unresectable locally advanced or metastatic solid tumors and confirmed MTAP loss receive oral vopimetostat (TNG462), an investigational PRMT5 inhibitor designed to exploit methylthioadenosine accumulation in MTAP-deleted tumors. Some cohorts receive it with the anti–PD-1 antibody pembrolizumab, including an NSCLC expansion cohort.
ClinicalTrials.gov ID: NCT05732831
