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

Primary Outcome Measures

1. Occurrence of Dose Limiting Toxicity [ Time Frame: over the first 21 days of dosing ]
   Incidence of Adverse and Serious Adverse Events
2. 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

Secondary Outcome Measures

1. Tumor Response [ Time Frame: through study completion, an average of 30 months ]
   Determined by RECIST v1.1 or modified RECIST v1.1
2. Pharmacokinetic Evaluation – Cmax [ Time Frame: over first 21 days of dosing ]
   Peak plasma concentration of VT3989
3. Pharmacokinetic Evaluation – Tmax [ Time Frame: over first 21 days of dosing ]
   Time to reach peak plasma concentration of VT3989
4. 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

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