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

• ClinicalTrials.gov Identifier: NCT04665206
• Recruitment Status: Recruiting
• First Posted: December 11, 2020
• Last Update Posted: May 3, 2023
• Sponsor: Vivace Therapeutics, Inc
• Information provided by (Responsible Party): Vivace Therapeutics, Inc

Tracking Information

• First Submitted Date: December 5, 2020
• First Posted Date: December 11, 2020
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: March 24, 2021
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 10, 2020)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 10, 2020)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors Enriched for Tumors With NF2 Gene Mutations
• Official Title: 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
• Brief Summary: 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.

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
• Study Phase: Phase 1

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Part 1 dose escalation: 3 + 3 design Part 2 dose expansion: up to 4 cohorts

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Solid Tumor, Adult
• Mesothelioma

Intervention

Drug: VT3989

25 or 100 mg capsules for oral administration.

Study Arms

• 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
  Intervention: Drug: VT3989
• 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.
  Intervention: Drug: VT3989

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 29, 2023): 188
• Original Estimated Enrollment (submitted: December 10, 2020): 80
• Estimated Study Completion Date: February 2024
• Estimated Primary Completion Date: February 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Heather Fritz; 650-627-7437; hfritz@inclin.com

Contact: Jill Abbey; 925-286-0832; jabbey@vivacetherapeutics.com

• Listed Location Countries: Australia, United States

Administrative Information

• NCT Number: NCT04665206
• Other Study ID Numbers: VT3989-001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Vivace Therapeutics, Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Vivace Therapeutics, Inc
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Vivace Therapeutics, Inc
• Verification Date: April 2023