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

Solid Tumor, Adult Clinical Trial

Official title:

Phase 1, Multi-Center, Open-Label Study of VT3989 in Patients With Refractory Locally Advanced or Metastatic Solid Tumors Enriched for Tumors Harboring Mutations of the Neurofibromatosis Type 2 Gene (Mutant NF2 or mNF2)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04665206
• Other study ID #: VT3989-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 24, 2021
• Est. completion date: June 2, 2027

Study information

• Verified date: May 2024
• Source: Vivace Therapeutics, Inc
• Contact: Heather Fritz
• Phone: 650-627-7437
• Email: hfritz[@]inclin.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: June 2, 2027
• Est. primary completion date: December 24, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

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

Related Conditions & MeSH terms

• Mesothelioma
• Solid Tumor, Adult

Intervention

Drug:
• VT3989
25, 50, 100,150 or 200 mg capsules for oral administration.

Locations

Country	Name	City	State
Australia	Monash Health	Clayton	Victoria
Australia	Peter MacCullum Cancer Centre	Melbourne	Victoria
Australia	Linear Clinical Research	Nedlands	Western Australia
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	Memorial Sloan Kettering Cancer Center-	New York	New York
United States	NEXT Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Vivace Therapeutics, Inc

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of Dose Limiting Toxicity	Incidence of Adverse and Serious Adverse Events	over the first 21 days of dosing
Primary	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	Tumor Response	Determined by RECIST v1.1 or modified RECIST v1.1	through study completion, an average of 30 months
Secondary	Pharmacokinetic Evaluation - Cmax	Peak plasma concentration of VT3989	over first 21 days of dosing
Secondary	Pharmacokinetic Evaluation - Tmax	Time to reach peak plasma concentration of VT3989	over first 21 days of dosing
Secondary	Pharmacokinetic Evaluation - Half-life	Time required for the plasma concentration of VT3989 to reduce by half after reaching peak	over first 21 days of dosing