Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors

NCT04665206 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: VT3989-001
• Study Type: interventional
• Target: 434
• Locations: 2 countries
• Sites: 12

Brief Summary

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.

Conditions

Solid Tumor, Adult; Mesothelioma; NSCLC

Outcome Measures

Primary Outcomes (2)

• Occurrence of Dose Limiting Toxicity

  Incidence of Adverse and Serious Adverse Events

  over the first 21 days of dosing

• Occurrence of General Toxicity

  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 Outcomes (7)

• Tumor Response

  through study completion, an average of 30 months

• Pharmacokinetic Evaluation - Cmax

  for first 6 cycles

• Pharmacokinetic Evaluation - Tmax

  for first 6 cycles

• Pharmacokinetic Evaluation - Half-life

  for first 6 cycles

• Overall survival

  At 6, 12, 18 and 24 months

Study Arms (3)

VT3989 Dose Escalation [Not Recruiting]

EXPERIMENTAL

VT3989 dosed orally in 21 or 28 day cycles. Patients will be enrolled into escalating dose levels during the Dose Escalation Phase

Drug: VT3989

Dose Expansion [Not Recruiting]

EXPERIMENTAL

VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma.

Drug: VT3989

Combination [Recruiting]

EXPERIMENTAL

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: VT3989; Drug: Nivolumab & Ipilimumab; Drug: Osimertinib; Drug: Pemetrexed/Carboplatin

Interventions

Pemetrexed/Carboplatin DRUG

Pemetrexed infusion: 500 mg/m2 intravenous infusion Carboplatin infusion: AUC 5.0 intravenous infusion

Combination [Recruiting]

VT3989 DRUG

25, 50, 100, 150 or 200 mg capsules for oral administration.

Combination [Recruiting]; Dose Expansion [Not Recruiting]; VT3989 Dose Escalation [Not Recruiting]

Nivolumab & Ipilimumab DRUG

Nivolumab infusion - 360 mg every 3 weeks, 30-minute intravenous infusion Ipilimumab infusion - 1 mg/kg every 6 weeks, 30-minute intravenous infusion

Combination [Recruiting]

Osimertinib DRUG

40 or 80 mg tablets for oral administration

Combination [Recruiting]

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Vivace Therapeutics, Inc: lead

Study Sites (12)

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94158, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

Virginia Cancer Specialists, PC

Arlington, Virginia, 22201, United States

RECRUITING

Monash Health

Clayton, Victoria, 3168, Australia

RECRUITING

Peter MacCullum Cancer Centre

Melbourne, Victoria, 3000, Australia

RECRUITING

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

RECRUITING

Related Publications (1)

• Yap TA, Kwiatkowski DJ, Dagogo-Jack I, Offin M, Zauderer MG, Kratzke R, Desai J, Body A, Millward M, Tolcher AW, Raghav KPS, Thurston A, Post L, Dorr FA, Tang TT, Li Y, Sharma N, Kindler HL. YAP/TEAD inhibitor VT3989 in solid tumors: a phase 1/2 trial. Nat Med. 2025 Dec;31(12):4281-4290. doi: 10.1038/s41591-025-04029-3. Epub 2025 Oct 19.

  PMID: 41111090 DERIVED

MeSH Terms

Conditions

Mesothelioma

Interventions

Nivolumab; Ipilimumab; osimertinib; Pemetrexed; Carboplatin

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Officials

• Neelesh Sharma, MD

  Vivace Therapeutics

  STUDY DIRECTOR

Central Study Contacts

Heather Fritz

CONTACT

650-627-7437; hfritz@inclin.com

Neelesh Sharma, MD

CONTACT

732-476-4978; nsharma@vivacetherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Part 1 dose escalation: 3 + 3 design Part 2 dose expansion: up to 6 cohorts Part 3 combination: 3 cohorts

Study Record Dates

• First Submitted: December 5, 2020
• First Posted: December 11, 2020
• Study Start: March 24, 2021
• Primary Completion (Estimated): November 2, 2029
• Study Completion (Estimated): March 2, 2030
• Last Updated: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3); US (9)