Editing Clinical Trials (section)

== What Targeted Therapies Are Showing Promise? ==

=== VT3989 TEAD Inhibitor — Advancing to Phase III ===

VT3989 represents a breakthrough in targeting the previously "undruggable" Hippo/YAP/TEAD pathway, which is dysregulated in the majority of mesotheliomas.<ref>[https://mesotheliomaattorney.com/mesothelioma/treatment/new/ New Mesothelioma Treatments], MesotheliomaAttorney.com</ref>

'''ESMO 2025 Results (Published Nature Medicine December 2025):'''
* '''Objective response rate:''' 32% in 22 mesothelioma patients at optimized dose
* '''Disease control rate:''' 86% when incorporating optimal dose and UACR threshold
* '''Median progression-free survival:''' 10 months
* '''Duration of response:''' 8 patients on treatment more than 1 year; one approaching 2 years
* '''Selected dose:''' 100 mg two-weeks-on/two-weeks-off for Phase III
* '''Safety:''' Favorable profile with mostly grade 1-2 toxicities; proteinuria reversible with dose adjustment
* '''Tumor types:''' Activity demonstrated in both NF2-mutant and wild-type tumors

'''Regulatory Designations:'''
* FDA Orphan Drug Designation
* FDA Fast Track Designation

{| style="width:100%; background:#cce5ff; border:1px solid #007bff; border-left:5px solid #007bff; border-radius:4px; margin:1em 0;"
|-
| style="padding:15px; color:#004085;" | '''ℹ️ Historic Milestone:''' VT3989 will become the '''first TEAD inhibitor to reach a registrational Phase III trial''' in mesothelioma when it opens in the first half of 2026, representing a major advance for targeted therapy in this disease.
|}

=== ISM6331 — First AI-Designed Drug for Mesothelioma (NCT06566079) ===

This pan-TEAD inhibitor was designed using Insilico Medicine's Chemistry42 AI platform, representing the first AI-designed drug to enter clinical testing for mesothelioma.<ref>[https://www.mesotheliomalawyercenter.org/mesothelioma/treatment/ Mesothelioma Treatment Options], Mesothelioma Lawyer Center</ref>

'''Development Timeline:'''
* '''September 2020:''' AI platform launched
* '''June 2023:''' Recommended for preclinical studies
* '''April 2024:''' AACR presentation showing broad cancer-killing effects
* '''June 2024:''' FDA Orphan Drug Designation granted
* '''August 2024:''' IND clearance received
* '''January 22, 2025:''' First patient dosed in China
* '''2026:''' US enrollment expected

'''Mechanism:''' Pan-TEAD inhibitor blocking the palmitoylation site, disrupting YAP/TAZ-TEAD transcriptional activity

=== IAG933 TEAD Inhibitor — Development Discontinued ===

Novartis discontinued development of IAG933 in October 2025 following underwhelming ESMO 2025 data showing only 13% objective response rate in 30 pleural mesothelioma patients. QTc prolongation dose-limiting toxicities in 4 patients contributed to the decision.<ref>[https://www.mesotheliomalawyercenter.org/mesothelioma/diagnosis/ Mesothelioma Diagnosis], Mesothelioma Lawyer Center</ref>