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

• Sponsor: Vivace Therapeutics, Inc (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT04665206
• Collaborator: (none)
• Enrollment: 80
• Locations: 8
• Arms: 2
• Anticipated Duration (Months): 34.3
• Patients Per Site: 10
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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 patients with advanced pleural malignant mesothelioma and/or metastatic solid tumors that are resistant or refractory to standard therapy or for which no effective standard therapy is available.

Condition or Disease	Intervention/Treatment	Phase
Solid Tumor, Adult; Mesothelioma	Drug: VT3989	Phase 1

Detailed Description

Dose escalation will employ a traditional 3 + 3 design to assess safety of VT3989 in patients with refractory metastatic solid tumors or advanced malignant pleural mesothelioma until the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is determined. The RP2D may be less than the MTD depending on the type and severity of AEs that occur during and after the first cycle.

In Dose Expansion, patients will be enrolled into 2 cohorts: Cohort 1 - malignant pleural mesothelioma patients with mutations of NF2 that have progressed on or following standard therapy; and Cohort 2 - solid tumor patients with mutations of NF2 that have progressed on or following standard therapy. Patients will be treated at the MTD or RP2D identified in Part 1, to provide further characterization of the safety, tolerability, efficacy, and biological activity of VT3989.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 80 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Part 1 dose escalation: 3 + 3 design Part 2 dose expansion: 2 parallel cohortsPart 1 dose escalation: 3 + 3 design Part 2 dose expansion: 2 parallel cohorts
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Mar 24, 2021
• Anticipated Primary Completion Date: Feb 1, 2024
• Anticipated Study Completion Date: Feb 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VT3989 Dose Escalation VT3989 dosed orally in 21 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 day cycles in patients with refractory metastatic solid tumors, or advanced pleural malignant mesothelioma, with NF2 mutant tumors.	Drug: VT3989; 25 or 100 mg capsules for oral administration.

Outcome Measures

Primary Outcome Measures

1. Occurrence of Dose Limiting Toxicity [over the first 21 days of dosing]

   Incidence of Adverse and Serious Adverse Events

2. 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

Secondary Outcome Measures

1. Tumor Response [through study completion, an average of 30 months]

   Determined by RECIST v1.1 or modified RECIST v1.1

2. Pharmacokinetic Evaluation - Cmax [over first 21 days of dosing]

   Peak plasma concentration of VT3989

3. Pharmacokinetic Evaluation - Tmax [over first 21 days of dosing]

   Time to reach peak plasma concentration of VT3989

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Part 1: pathologically diagnosed metastatic solid tumor or advanced malignant pleural mesothelioma that has progressed on or after standard of care therapy with evaluable or measurable disease per RECIST v1.1

• Part 2: pathologically diagnosed advanced malignant pleural mesothelioma with NF2 mutations (Cohort 1) or metastatic solid tumors with NF2 mutation (Cohort 2), for which there is no further standard of care therapy available with measurable disease per RECIST v1.1 for solid tumors 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago Medical Center	Chicago	Illinois	United States	60637
2	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
4	MD Anderson Cancer Center	Houston	Texas	United States	77030
5	NEXT Oncology	San Antonio	Texas	United States	78229
6	Monash Health	Clayton	Victoria	Australia	3168
7	Peter MacCullum Cancer Centre	Melbourne	Victoria	Australia	3000
8	Linear Clinical Research	Nedlands	Western Australia	Australia	6009

Sponsors and Collaborators

• Vivace Therapeutics, Inc

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Vivace Therapeutics, Inc
• ClinicalTrials.gov Identifier: NCT04665206
• Other Study ID Numbers: VT3989-001
• First Posted: Dec 11, 2020
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Mesothelioma

Study Results

No Results Posted as of Nov 2, 2021