Key trial information from research of VT3989. Credit score: The College of Texas MD Anderson Most cancers Middle
The primary-in-class YAP-TEAD inhibitor VT3989 continued to be properly tolerated and demonstrated notable preliminary antitumor exercise, significantly in sufferers with refractory mesothelioma, in response to outcomes from a trial led by researchers from The College of Texas MD Anderson Most cancers Middle.
Information from the Section I/II trial have been offered in the present day by Timothy Yap, M.B.B.S., Ph.D., professor of Investigational Most cancers Therapeutics and vp and head of scientific improvement of MD Anderson’s Therapeutics Discovery division, on the 2025 European Society for Medical Oncology (ESMO) Congress and revealed concurrently in Nature Medication.
What are the notable outcomes of this research evaluating VT3989?
The trial enrolled 172 sufferers, together with 135 with refractory mesothelioma. Of the 22 mesothelioma sufferers handled with the optimized dose ranges, seven had partial responses and 12 had steady illness—a illness management price of 86%. All 22 mesothelioma sufferers had beforehand obtained immunotherapy, and 82% had beforehand obtained chemotherapy.
“This study has multiple important takeaways, including the demonstration of significant disease control even in this heavily pretreated population,” Yap mentioned. “The safety profile was also encouraging, with mainly low-grade adverse effects. These data were strong enough to support the continued clinical development of VT3989 in mesothelioma, and we look forward to the next clinical study of the compound.”
How does VT3989 work?
This trial of VT3989 represents the primary scientific proof-of-concept for inhibiting a part of an vital signaling pathway that regulates cell development and immune response. This pathway is named the Hippo signaling pathway and, inside this pathway, the yes-associated proteins (YAP) work with transcriptional enhancer activator area (TEAD) proteins.
In a number of most cancers varieties, YAP is overexpressed or overactivated attributable to dysfunction within the pathway, which fuels most cancers development. VT3989 inhibits a selected modification on the TEAD protein, which blocks YAP operate. Therefore, VT3989 is named a YAP-TEAD inhibitor.
Why is that this being studied in mesothelioma sufferers?
Cancers with NF2 gene mutations are significantly depending on the YAP-TEAD pathway. The NF2 gene encodes a protein referred to as Merlin, and NF2 gene mutations/Merlin protein loss are frequent in mesothelioma sufferers.
Moreover, mesothelioma is a most cancers that could be very tough to deal with, and there are at present restricted choices for sufferers who don’t reply to first-line remedies, making this a serious unmet scientific want.
Preliminary information from this trial have been offered on the American Affiliation for Most cancers Analysis (AACR) Annual Assembly 2023, demonstrating encouraging Section I outcomes.
Extra info:
YAP/TEAD inhibitor VT3989 in stable tumours: a part 1/2 trial, Nature Medication (2025). www.nature.com/articles/s41591-025-04029-3
Supplied by
College of Texas M. D. Anderson Most cancers Middle
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VT3989 continues to point out promising early ends in sufferers with superior mesothelioma (2025, October 19)
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