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

Phase 1, Multi-Center, Open-Label, Study to Evaluate the Safety, Tolerability, and PK of VT3989 in Patients With Refractory Locally Advanced or Metastatic Solid Tumors Enriched for Tumors Harboring Mutations of the NF2 Gene

This is an open-label, dose escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered 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.

Study Overview

• Status: Recruiting
• Conditions: Mesothelioma; Solid Tumor, Adult
• Intervention / Treatment: Drug: VT3989

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 until until the MTD or recommended phase 2 dose(s) and schedule(s) are determined. The recommended phase 2 dose(s) and schedule(s) may be less than the MTD depending on the type and severity of AEs that occur during and after the first cycle.

Dose Expansion patients will be enrolled into up to 4 cohorts: Cohorts 1 and 2 will both enroll mesothelioma patients with or without an NF2 mutation that have progressed following standard therapy. The cohorts will differ by either the dose and/or schedule of VT3989, as recommended by the SRC. If a 3rd expansion cohort for mesothelioma patients is enrolled, it will employ a different regimen than the initial 2 expansion cohorts. If an NF2m solid tumor cohort is evaluated, it will use one of the regimens evaluated in the mesothelioma expansion cohorts.

• Study Type: Interventional
• Enrollment (Estimated): 188
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Heather Fritz; Phone Number: 650-627-7437; Email: hfritz@inclin.com
• Study Contact Backup: Name: Neelesh Sharma; Phone Number: 732-476-4978; Email: nsharma@vivacetherapeutics.com

Study Locations

• Australia
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Recruiting
      • Monash Health
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCullum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research
• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center-
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson Cancer Center
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 documented NF2 mutations.
• 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
• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VT3989 Dose Escalation; 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 or 100 mg capsules for oral administration.
Experimental: Dose Expansion; VT3989 dosed in 21 or 28 day cycles in patients with refractory metastatic solid tumors or mesothelioma, with or without NF2 mutant tumors.	Drug: VT3989; 25 or 100 mg capsules for oral administration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor Response	Determined by RECIST v1.1 or modified RECIST v1.1	through study completion, an average of 30 months
Pharmacokinetic Evaluation - Cmax	Peak plasma concentration of VT3989	over first 21 days of dosing
Pharmacokinetic Evaluation - Tmax	Time to reach peak plasma concentration of VT3989	over first 21 days of dosing
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

Collaborators and Investigators

• Sponsor: Vivace Therapeutics, Inc

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2021
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

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 (Estimated): February 13, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Adenoma; Neoplasms, Mesothelial; Mesothelioma
• 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