A Phase 1/2, Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Anti-tumor Activity of TNG462 as a Single Agent and in Combination in Patients With MTAP-deleted Advanced or Metastatic Solid Tumors

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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

Inclusion Criteria:

1. Age: ≥18 years-of-age at the time of signature of the main study ICF

2. Performance status: ECOG Performance Score of 0 to 1

3. Confirmed histologic or cytologic diagnosis of a locally advanced, metastatic, and/or unresectable solid tumor

4. Prior standard therapy, as available

5. Documented bi-allelic (homozygous) deletion of MTAP in a tumor detected by next- generation sequencing or absence of MTAP protein in a tumor detected by IHC.

6. Adequate organ function/reserve per local labs

7. Adequate liver function per local labs

8. Adequate renal function per local labs

9. Negative serum pregnancy test result at screening

10. Written informed consent must be obtained according to local guidelines

Exclusion Criteria:

1. Known allergies, hypersensitivity, or intolerance to TNG462, or its excipients or to pembrolizumab in the combination treatment arms

2. Uncontrolled intercurrent illness that will limit compliance with the study requirements

3. Active infection requiring systemic therapy

4. Currently participating in or has planned participation in a study of another investigational agent or device

5. Impairment of GI function or disease that may significantly alter the absorption of oral TNG462

6. Active prior or concurrent malignancy.

7. Central nervous system metastases associated with progressive neurological symptoms

8. Current active liver disease from any cause

9. Known to be HIV positive, unless all of the following criteria are met:

1. CD4+ count ≥300/μL

2. Undetectable viral load

3. Receiving highly active antiretroviral therapy

10. Clinically relevant cardiovascular disease

11. A female patient who is pregnant or lactating

12. Patient is unwilling or unable to comply with the scheduled visits, drug administration plan, laboratory tests, biopsy, or other study procedures and study restrictions

13. Patient has a prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, or laboratory abnormality that, in the investigator's opinion, may affect the safety of the patient or impair the assessment of study results