Study to Evaluate VT3989 in Patients With Metastatic Solid Tumors

Inclusion Criteria

• Part 1: Patients with pathologically diagnosed metastatic solid tumor or mesothelioma who have 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 Expansion Cohorts 1 and 2: In mesothelioma cohorts, patients with pathologically diagnosed advanced malignant mesothelioma with or without NF2 mutations, who have 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 Expansion Cohort 3: Only non-pleural mesothelioma patients with epithelioid histology, who have relapsed from or are refractory to prior platinum-based chemotherapy and immunotherapy.
• Part 2 Expansion Cohort 4: in the solid tumor cohort, patients with pathologically diagnosed metastatic or locally advanced solid tumor with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements, who have progressed on or after approved therapies of known clinical benefit except if the patient refuses or is not a candidate for such therapy.
• Part 2 Expansion Cohort 5: Patients with pathologically diagnosed advanced malignant pleural mesothelioma with epithelioid histology, who have progressed on or after licensed immunotherapy, chemotherapy or combined chemoimmunotherapy, except if the patient refuses or is not a candidate for such therapy.
• Part 3 Combination Cohort A: Patients with pathologically diagnosed, metastatic or unresectable malignant mesothelioma (including both pleural and non-pleural) who have not received systemic therapy.
• Part 3 Combination Cohort B: Patients with pathologically diagnosed incurable locally advanced (inoperable or recurrent), or metastatic NSCLC with exon 19 deletions or exon 21 L858R mutations, with or without prior treatment with Osimertinib.
• Part 1: Evaluable or measurable disease per RECIST v1.1 or mRECIST
• Part 2 and 3: Measurable disease per RECIST v1.1 for non-pleural mesothelioma or other solid tumors or modified RECIST v1.1 for malignant pleural mesothelioma. mRECIST may be used for pleural extension of non-pleural mesothelioma or for mixed pleural and peritoneal (or other) mesothelioma.
• ECOG: 0-1.
• Adequate organ functions, including the liver, kidneys, and hematopoietic system.

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
• Known HIV positive or active Hepatitis B or Hepatitis C
• Clinically significant cardiovascular disease
• Corrected QT (QTcF) interval > 470 msec (using Fridericia's correction formula); except for Part 2 Expansion Cohort 3, the QTcF interval criteria is > 450 msec).
• Additional active malignancy that may confound the assessment of the study endpoints
• Women who are pregnant or breastfeeding
• Prior treatment with TEAD inhibitor, except for EHE patients.