2023 World Conference on Lung Cancer (Posters)-P2.19. First-in-Human Phase 1 Trial of VT3989, a First-in-Class YAP/TEAD Inhibitor in Patients with Advanced Mesothelioma

P2.19. First-in-Human Phase 1 Trial of VT3989, a First-in-Class YAP/TEAD Inhibitor in Patients with Advanced Mesothelioma - PDF(Abstract)

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This document provides a summary of a clinical trial in progress for a first-in-human Phase 1 trial of VT3989, a YAP/TEAD inhibitor, in patients with advanced mesothelioma. The study aims to evaluate the safety, tolerability, recommended Phase 2 dose (RP2D), antitumor activity, pharmacokinetics, and the correlation of NF2 mutations and other alterations with response. 69 patients were enrolled, including 44 with mesothelioma. The patients had a median age of 65 and had received multiple prior regimens, including platinum and pemetrexed, immune checkpoint inhibitors, and VEGF antibodies. The most common adverse events were reversible albuminuria and peripheral edema. The study found that VT3989 was well tolerated, with no dose-limiting toxicities observed. Six mesothelioma patients achieved partial responses, with three responses ongoing up to 21 months. The responders had epithelioid histology, and two of them had NF2 mutations. The study concluded that VT3989 is well tolerated with durable responses in patients with refractory mesothelioma, providing clinical proof-of-concept for drugging the Hippo-YAP-TEAD pathway. Further optimization of the RP2D and exploration of different intermittent schedules are ongoing. Overall, the study demonstrates promising results for VT3989 in treating advanced mesothelioma.

Asset Subtitle

Timothy Yap

Meta Tag

Speaker Timothy Yap

Topic Mesothelioma, Thymoma & Other Thoracic Tumors: Clinical Trial in Progress

Keywords

clinical trial

VT3989

advanced mesothelioma

safety

tolerability

antitumor activity

NF2 mutations

partial responses

refractory mesothelioma

promising results