A Phase 3 Trial in Advanced Epithelioid Mesothelioma (sTEADfast)

A Phase 3, Randomized, Open-label Trial Comparing VT3989 Versus Gemcitabine or Vinorelbine in Participants With Advanced Epithelioid Mesothelioma, Who Previously Received Platinum-Based Systemic Chemotherapy and Immunotherapy

This randomized, open-label, multicenter Phase 3 trial will compare VT3989 with Investigator's choice of gemcitabine or vinorelbine in adults with advanced epithelioid pleural mesothelioma whose disease progressed after prior platinum-based systemic chemotherapy and immunotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Mesothelioma; Pleural Mesothelioma
• Intervention / Treatment: Drug: VT3989; Drug: gemcitabine; Drug: Vinorelbine

Detailed Description

Approximately 350 participants will be randomized 1:1 to VT3989 (Arm A) or Investigator's choice chemotherapy with gemcitabine or vinorelbine (Arm B).

VT3989 will be administered orally at 100 mg once daily for 2 weeks on treatment followed by 2 weeks off treatment in each 4-week cycle. Comparator treatment will be gemcitabine or vinorelbine using the protocol-specified regimen or local prescribing/institutional practice.

The trial includes screening, treatment, safety follow-up, and survival follow-up periods. A QTc Sub-Study will evaluate cardiac repolarization using time-matched pharmacokinetic samples and ECGs in approximately 25 Arm A participants. Overall survival is the primary endpoint; BICR-assessed progression-free survival is the key secondary endpoint.

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Arick Wong; Phone Number: 650-666-2753; Email: vt3989-003@vivacetherapeutics.com
• Study Contact Backup: Name: Dereck Amakye; Phone Number: 650-666-2753; Email: info@vivacetherapeutics.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, age 18 years or older at informed consent.
• Pathologically confirmed advanced epithelioid pleural mesothelioma previously treated with platinum-based systemic chemotherapy and immunotherapy, given sequentially or concurrently.
• Radiologically measurable disease by modified RECIST v1.1 or RECIST v1.1.
• ECOG: 0-1.
• Adequate organ functions, including the liver, kidneys, and hematopoietic system.

Exclusion Criteria:

• Active brain metastases or primary CNS (central nervous system) tumors.
• History of leptomeningeal metastases
• Active or chronic, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• Known HIV positive or active Hepatitis B or Hepatitis C
• Clinically significant cardiovascular disease and prior exposure to cardiotoxic agents
• Corrected QT (QTcF) interval > 470 msec (using Fridericia's correction formula).
• Women who are pregnant or breastfeeding
• Non-pleural mesothelioma at initial diagnosis or an aggressive histologic type such as sarcomatoid or biphasic mesothelioma.
• Prior treatment with a TEAD inhibitor, including VT3989 or another agent targeting the same molecular pathway.
• Prior receipt of both comparator treatments, gemcitabine and vinorelbine, alone or in combination, or known hypersensitivity to both. A participant who received only one comparator may enroll but must not be assigned to that same comparator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A - VT3989; VT3989 monotherapy in 28-day cycles until BICR-verified progression, unacceptable toxicity, withdrawal, or another protocol-specified reason.	Drug: VT3989; • 100 mg orally once daily for 2 weeks on treatment followed by 2 weeks off treatment (2W/2W) in each 4-week cycle
Active Comparator: Arm B - Investigator's Choice Chemotherapy; The Investigator selects 21-day cycle of gemcitabine or vinorelbine. Administration and dose modification may follow the protocol, local prescribing information, or institutional practice.	Drug: gemcitabine; • 1,000 mg/m2 IV on Days 1 and 8 of each 3-week cycle, or per local prescribing information/institutional practice; Drug: Vinorelbine; • 25-30 mg/m2 IV on Days 1 and 8 of each 3-week cycle, or per local prescribing information/institutional practice

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Time from randomization to death from any cause. Participants without an observed death will be censored at the last date known alive or the analysis cut-off date, whichever is earlier.	Approximately 32-35 months after first randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival by BICR	Time from randomization to the first BICR-assessed radiologic progressive disease or death, using protocol-defined censoring rules.	From randomization through radiologic progression, death, up to approximately 3 years or more
Treatment-Emergent Adverse Events and Serious Adverse Events	Incidence and severity of Treatment-Emergent Adverse Events and Serious Adverse Events	From first dose through the safety follow-up visit, (28 days after the last dose), up to approximately 3 years or more.
Disease-related symptoms and health-related quality of life outcomes	Disease-related symptoms, treatment side effects, functioning, and health-related quality of life outcomes and time to deterioration.	Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more
Overall Response Rate by BICR	Overall Response Rate by BICR Proportion with best overall response of complete response or partial response by RECIST v1.1 and/or modified RECIST v1.1, assessed by BICR.	Tumor assessments during treatment and applicable follow-up; up to approximately 3 years or more
Duration of Response	Among participants with a complete or partial response, time from first documented response to progressive disease or death, with protocol-defined censoring.	From first documented response through progression, death, or analysis cut-off; up to approximately 3 years or more
Disease Control Rate by BICR	Proportion with best overall response of complete response, partial response, or stable disease by RECIST v1.1 and/or modified RECIST v1.1, assessed by BICR.	Tumor assessments during treatment and applicable follow-up; up to approximately 3 years or more
Time to Response	Time from randomization to the first documented complete or partial response by RECIST v1.1 and/or modified RECIST v1.1.	From randomization to first documented response; up to approximately 3 years or more
EORTC QLQ-LC13	Lung cancer- and treatment-related symptoms using the EORTC Quality of Life Questionnaire Lung Cancer Module 13.	Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more
EQ-5D-5L	Health status and health-related quality of life using the EuroQol 5 Dimension-5 Levels instrument.	Baseline through treatment and protocol-specified follow-up; up to approximately 3 years or more
Time to Deterioration	Time to protocol-defined deterioration in disease-related symptoms and health-related quality of life; detailed definition will be specified in the Statistical Analysis Plan.	From baseline/randomization through protocol-defined deterioration; up to approximately 3 years or more

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic Evaluation - Cmax	Peak plasma concentration of VT3989	Up to Cycle 9 (each cycle is 28 days)
Pharmacokinetic Evaluation - AUC	Area under the plasma concentration versus time curve (AUC)	Up to Cycle 9 (each cycle is 28 days)
Correlation between VT3989 exposure	Correlation between VT3989 exposure	Up to Cycle 9 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Vivace Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): January 1, 2031

Study Registration Dates

• First Submitted: September 1, 2026
• First Submitted That Met QC Criteria: September 11, 2026
• First Posted (Actual): September 17, 2026

Study Record Updates

• Last Update Posted (Actual): September 17, 2026
• Last Update Submitted That Met QC Criteria: September 11, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Mesothelioma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Adenoma; Neoplasms, Mesothelial; Pleural Neoplasms; Mesothelioma, Malignant; Mesothelioma; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indolizidines; Indolizines; Vinorelbine; Gemcitabine
• Other Study ID Numbers: VT3989-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No