Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors

NCT ID: NCT04665206

Last Updated: 2025-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

336 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-24

Study Completion Date

2027-06-02

Brief Summary

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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.

Detailed Description

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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 two 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).

Conditions

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Solid Tumor, Adult Mesothelioma NSCLC

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Part 1 dose escalation: 3 + 3 design Part 2 dose expansion: up to 6 cohorts Part 3 combination: 2 cohorts
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

VT3989

Intervention Type DRUG

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

Dose Expansion [Not Recruiting]

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

Group Type EXPERIMENTAL

VT3989

Intervention Type DRUG

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

Combination [Recruiting]

VT3989 dosed in 28 day cycles in patients with metastatic solid tumors or mesothelioma, in combination with immunotherapy (nivolumab/ipilimumab) or targeted therapy (osimertinib)

Group Type EXPERIMENTAL

VT3989

Intervention Type DRUG

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

Nivolumab & Ipilimumab

Intervention Type DRUG

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

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

Osimertinib

Intervention Type DRUG

40 or 80 mg tablets for oral administration

Interventions

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VT3989

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

Intervention Type 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

Intervention Type DRUG

Osimertinib

40 or 80 mg tablets for oral administration

Intervention Type DRUG

Eligibility Criteria

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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.
* 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
* Corrected QT (QTcF) interval \> 470 msec (using Fridericia's correction formula); except for Part 2 Expansion Cohort 3, the QTcF interval criteria is \> 450 msec).
* Additional active malignancy that may confound the assessment of the study endpoints
* Women who are pregnant or breastfeeding
* Prior treatment with TEAD inhibitor, except for EHE patients.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Vivace Therapeutics, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Neelesh Sharma, MD

Role: STUDY_DIRECTOR

Vivace Therapeutics

Locations

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UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Site Status RECRUITING

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

NEXT Oncology

San Antonio, Texas, United States

Site Status RECRUITING

Virginia Cancer Specialists, PC

Arlington, Virginia, United States

Site Status RECRUITING

Monash Health

Clayton, Victoria, Australia

Site Status RECRUITING

Peter MacCullum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Linear Clinical Research

Nedlands, Western Australia, Australia

Site Status RECRUITING

Countries

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United States Australia

Central Contacts

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Heather Fritz

Role: CONTACT

650-627-7437

Neelesh Sharma, MD

Role: CONTACT

732-476-4978

Facility Contacts

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Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

Heather Fritz

Role: primary

650-627-7437

References

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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 Oct 19. doi: 10.1038/s41591-025-04029-3. Online ahead of print.

Reference Type DERIVED
PMID: 41111090 (View on PubMed)

Other Identifiers

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VT3989-001

Identifier Type: -

Identifier Source: org_study_id

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