Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors

March 27, 2026 updated by: Vivace Therapeutics, Inc

Phase I/II, Multi-Center, Open-Label Study of VT3989, Alone or in Combination, in Patients With Locally Advanced or Metastatic Solid Tumors

This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered, alone or in combination, once daily in patients with mesothelioma and/or metastatic solid tumors that are resistant to standard therapy or for which no effective standard therapy is available.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Dose escalation (Part 1) will employ a traditional 3 + 3 design to assess safety of VT3989 in patients with metastatic solid tumors or mesothelioma. The 3 + 3 design will be implemented until the MTD or recommended phase 2 dose(s) and schedule(s) are determined. The MTD is defined as the highest dose level at which < 33% of patients experience a dose limiting toxicity (DLT) during the first cycle of the study (Cycle 1).

Dose Expansion (Part 2) will further evaluate the safety and assess preliminary antitumor activity at the recommended phase 2 dose(s) and schedule(s) with up to 6 cohorts. Expansion cohorts 1 and 2 will enroll patients with mesothelioma of any site origin with or without NF2 mutations. Expansion cohort 3 will enroll non-pleural mesothelioma patients. Expansion cohort 4 will enroll solid tumor patients with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements. Cohort 5 will enroll pleural mesothelioma patients.

Combination part (Part 3) includes three cohorts. Cohort A will enroll mesothelioma patients who will receive VT3989 in combination with immunotherapy (nivolumab plus ipilimumab). Cohort B will enroll NSCLC patients whose tumors have exon 19 deletion or exon 21 L858R mutation and will receive VT3989 in combination with targeted therapy (Osimertinib). Cohort C will enroll mesothelioma patients who will receive VT3989 in combination with chemotherapy (pemetrexed plus carboplatin).

Study Type

Interventional

Enrollment (Estimated)

434

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Australia
    • Victoria
      • Clayton, Victoria, Australia, 3168
        • Recruiting
        • Monash Health
        • Contact:
      • Melbourne, Victoria, Australia, 3000
        • Recruiting
        • Peter MacCullum Cancer Centre
        • Contact:
    • Western Australia
      • Nedlands, Western Australia, Australia, 6009
        • Recruiting
        • Linear Clinical Research
        • Contact:
  • United States
    • California
      • San Francisco, California, United States, 94158
        • Recruiting
        • UCSF Helen Diller Family Comprehensive Cancer Center
        • Contact:
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Recruiting
        • University of Chicago Medical Center
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Contact:
      • Boston, Massachusetts, United States, 02215
        • Recruiting
        • Dana-Farber Cancer Institute
        • Contact:
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • M Health Fairview University of Minnesota Medical Center
        • Contact:
    • New York
      • New York, New York, United States, 10065
        • Recruiting
        • Memorial Sloan Kettering Cancer Center
        • Contact:
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
        • Contact:
      • San Antonio, Texas, United States, 78229
        • Recruiting
        • NEXT Oncology
        • Contact:
    • Virginia
      • Arlington, Virginia, United States, 22201
        • Recruiting
        • Virginia Cancer Specialists, PC
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Part 3 Combination Cohort A: Patients with pathologically diagnosed, metastatic or unresectable malignant mesothelioma (including both pleural and non-pleural) who have not received systemic therapy.
  • Part 3 Combination Cohort B: Patients with pathologically diagnosed incurable locally advanced (inoperable or recurrent), or metastatic NSCLC with exon 19 deletions or exon 21 L858R mutations, with or without prior treatment with Osimertinib.
  • Part 3 Combination Cohort C: Patients with pathologically diagnosed metastatic or unresectable malignant pleural mesothelioma who have not received systemic chemotherapy.
  • Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors or modified RECIST v1.1 for malignant pleural mesothelioma. mRECIST may be used for pleural extension of non-pleural mesothelioma or for mixed pleural and peritoneal (or other) mesothelioma.
  • 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).
  • Additional active malignancy that may confound the assessment of the study endpoints
  • Women who are pregnant or breastfeeding
  • Prior treatment with TEAD inhibitor.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: VT3989 Dose Escalation [Not Recruiting]
VT3989 dosed orally in 21 or 28 day cycles. Patients will be enrolled into escalating dose levels during the Dose Escalation Phase
Drug: VT3989
25, 50, 100, 150 or 200 mg capsules for oral administration.
Experimental: Dose Expansion [Not Recruiting]
VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma.
Drug: VT3989
25, 50, 100, 150 or 200 mg capsules for oral administration.
Experimental: Combination [Recruiting]
For Cohort A and B, VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib). For Cohort C, VT3989 dosed in 21 day cycles in patients with mesothelioma in combination with chemotherapy (pemetrexed+carboplatin) for 4-6 cycles, then continuing VT3989 as monotherapy on 28-day cycle.
Drug: Nivolumab & Ipilimumab

Nivolumab infusion - 360 mg every 3 weeks, 30-minute intravenous infusion

Ipilimumab infusion - 1 mg/kg every 6 weeks, 30-minute intravenous infusion

Drug: Osimertinib
40 or 80 mg tablets for oral administration
Drug: VT3989
25, 50, 100, 150 or 200 mg capsules for oral administration.
Drug: Pemetrexed/Carboplatin
Pemetrexed infusion: 500 mg/m2 intravenous infusion Carboplatin infusion: AUC 5.0 intravenous infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of Dose Limiting Toxicity
Time Frame: over the first 21 days of dosing
Incidence of Adverse and Serious Adverse Events
over the first 21 days of dosing
Occurrence of General Toxicity
Time Frame: through study completion, an average of 30 months
Incidence of Adverse and Serious Adverse Events, Discontinuations due to Adverse Events and general safety evaluations
through study completion, an average of 30 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Tumor Response
Time Frame: through study completion, an average of 30 months
Determined by RECIST v1.1 or modified RECIST v1.1
through study completion, an average of 30 months
Pharmacokinetic Evaluation - Cmax
Time Frame: for first 6 cycles
Peak plasma concentration of VT3989
for first 6 cycles
Pharmacokinetic Evaluation - Tmax
Time Frame: for first 6 cycles
Time to reach peak plasma concentration of VT3989
for first 6 cycles
Pharmacokinetic Evaluation - Half-life
Time Frame: for first 6 cycles
Time required for the plasma concentration of VT3989 to reduce by half after reaching peak
for first 6 cycles
Quality of life assessment (Part 2, expansion cohort 3, 4, and 5)
Time Frame: Through study completion, an average of 30 months
Assessing the Quality of life changes via patient reported outcomes
Through study completion, an average of 30 months
Overall survival
Time Frame: At 6, 12, 18 and 24 months
The overall survival of the enrolled patients from starting VT3989 treatment
At 6, 12, 18 and 24 months
Progression free survival
Time Frame: At 6, 12, 18 and 24 months
The progression free survival of the enrolled patients from starting VT3989 treatment
At 6, 12, 18 and 24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vivace Therapeutics, Inc

Investigators

  • Study Director: Neelesh Sharma, MD, Vivace Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 24, 2021

Primary Completion (Estimated)

November 2, 2029

Study Completion (Estimated)

March 2, 2030

Study Registration Dates

First Submitted

December 5, 2020

First Submitted That Met QC Criteria

December 10, 2020

First Posted (Actual)

December 11, 2020

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • VT3989-001

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

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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