Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors Enriched for Tumors With NF2 or mNF2 Gene Mutations

Phase 1

Recruiting

• Conditions: Solid Tumor, Adult; Mesothelioma
• Interventions: Drug: VT3989

• Registration Number: NCT04665206
• Lead Sponsor: Vivace Therapeutics, Inc

Brief Summary

This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered once daily in 3- or 4-week cycles in patients with mesothelioma and/or metastatic solid tumors that are resistant or refractory to standard therapy or for which no effective standard therapy is available.

Detailed Description

Dose escalation will employ a traditional 3 + 3 design to assess safety of VT3989 in patients with refractory 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 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 using optimal 2-stage Simon designs. 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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations
|
Related News

Study Timeline

• Study First Submitted: 2020-12-05
• Study First Submitted QC: 2020-12-10
• Study First Posted: 2020-12-11
• Study Start: 2021-03-24
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-09
• Last Update Posted: 2024-05-13
• Primary Completion: 2026-12-24
• Study Completion: 2027-06-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

• Part 1: pathologically diagnosed metastatic solid tumor or mesothelioma that has progressed on or after all approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy;
• Part 2: In mesothelioma cohorts, pathologically diagnosed advanced malignant mesothelioma with or without NF2 mutations, that has progressed on or after all approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy. In the solid tumor cohort, pathologically diagnosed solid tumor with with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements, which have progressed on or after approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy.
• Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors (solid tumor expansion cohort) or modified RECIST v1.1 for malignant pleural mesothelioma.
• ECOG: 0-1

Read More

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
• HIV positive or active Hepatitis B or Hepatitis C
• Clinically significant cardiovascular disease
• Additional active malignancy that may confound the assessment of the study endpoints
• Women who are pregnant or breastfeeding
• Prior treatment with TEAD inhibitor

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
VT3989 Dose Escalation	VT3989	VT3989 dosed orally in 21 or 28 day cycles. Patients will be enrolled into escalating dose levels during the Dose Escalation Phase
Dose Expansion	VT3989	VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma, with or without NF2 mutant tumors.

Primary Outcome Measures

Name	Time	Method
Occurrence of General Toxicity	through study completion, an average of 30 months	Incidence of Adverse and Serious Adverse Events, Discontinuations due to Adverse Events and general safety Evaluations
Occurrence of Dose Limiting Toxicity	over the first 21 days of dosing	Incidence of Adverse and Serious Adverse Events

Secondary Outcome Measures

Name	Time	Method
Tumor Response	through study completion, an average of 30 months	Determined by RECIST v1.1 or modified RECIST v1.1
Pharmacokinetic Evaluation - Cmax	over first 21 days of dosing	Peak plasma concentration of VT3989
Pharmacokinetic Evaluation - Tmax	over first 21 days of dosing	Time to reach peak plasma concentration of VT3989
Pharmacokinetic Evaluation - Half-life	over first 21 days of dosing	Time required for the plasma concentration of VT3989 to reduce by half after reaching peak

Trial Locations

Locations (9)

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Linear Clinical Research; 🇦🇺 Nedlands, Western Australia, Australia

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Peter MacCullum Cancer Centre; 🇦🇺 Melbourne, Victoria, Australia

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

Dana-Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Monash Health; 🇦🇺 Clayton, Victoria, Australia

Memorial Sloan Kettering Cancer Center-; 🇺🇸 New York, New York, United States

NEXT Oncology; 🇺🇸 San Antonio, Texas, United States