VT3989 Doubles Time Without Progression

A new class of cancer drug has shown unprecedented results in mesothelioma patients who have exhausted standard treatments. VT3989, developed by Vivace Therapeutics, more than doubled the time patients lived without their cancer progressing compared to salvage chemotherapy.

What Is VT3989?

VT3989 is the first drug to successfully target the Hippo signaling pathway, a cellular mechanism that, when disrupted, allows cancer cells to grow unchecked.

How It Works

The drug inhibits a protein called TEAD by blocking a process called autopalmitoylation. In simple terms:

1. Normal cells use the Hippo pathway to control growth
2. Mesothelioma cells often have defects that disable this “brake”
3. VT3989 reactivates the brake by blocking TEAD, stopping cancer growth

This mechanism is entirely different from chemotherapy or immunotherapy, potentially offering benefit even when those treatments have failed.

ESMO 2025 Trial Results

Results from the Phase I/II trial were presented at the European Society for Medical Oncology (ESMO) Congress in September 2025 and published in Nature Medicine.

Patient Population

All mesothelioma patients in the optimized dose group had already failed immunotherapy, meaning this drug worked in patients with limited remaining options.

Efficacy Data

Among the 22 mesothelioma patients treated at the optimized dose:

The 86% disease control rate is remarkable for a population that had already progressed through first-line treatments.

Survival Comparison

Patients on VT3989 went more than twice as long without their cancer worsening compared to standard third-line chemotherapy.

Safety Profile

VT3989 was generally well tolerated, with mostly low-grade side effects:

*UACR = Urine Albumin-to-Creatinine Ratio

Key safety findings:

• No dose-limiting toxicities across 172 patients
• Only 3.5% discontinued due to adverse events
• Proteinuria was reversible with dose reduction
• No kidney function impairment or nephrotic syndrome

Dosing Innovation

VT3989 has a long half-life of 9 days, allowing for intermittent dosing:

• Schedule: 100 mg, 2 weeks on / 2 weeks off
• Benefit: Limits drug accumulation while maintaining effectiveness
• Practicality: Oral medication, taken at home

FDA Designations

The FDA has granted VT3989 two special designations for mesothelioma:

Fast Track designation specifically applies to patients with unresectable mesothelioma whose disease progressed after both immunotherapy and chemotherapy.

Path to Approval

Timeline

Vivace Therapeutics plans to begin a registrational Phase 3 trial in the first half of 2026, which could lead to FDA approval within 3-4 years.

What This Means for Patients

For Patients Who’ve Failed Immunotherapy

VT3989 represents the first drug to show meaningful activity specifically in patients whose mesothelioma progressed after immunotherapy. Currently, options for these patients are limited to:

• Salvage chemotherapy (median PFS ~15 weeks)
• Clinical trials
• Best supportive care

VT3989 more than doubles progression-free survival in this population.

How to Access VT3989

Currently, VT3989 is only available through clinical trials. Patients interested in access should:

1. Ask their oncologist about open trials
2. Check ClinicalTrials.gov for VT3989 mesothelioma studies
3. Contact Vivace Therapeutics for trial information

The Bigger Picture: Hippo Pathway

VT3989’s success validates the Hippo pathway as a therapeutic target. Other companies have tried and failed to develop TEAD inhibitors:

• Novartis (IAG933): Discontinued development in 2025
• Other programs: Mixed results

VT3989 appears to have a differentiated mechanism that avoids problems that plagued other drugs in this class.

Comparison to Current Treatments

While overall survival data mature, the dramatic PFS improvement suggests VT3989 could become a new standard for refractory mesothelioma.