Brief Summary
This is an open-label, dosethe amount of medication taken escalation and expansion study to evaluate the safety, tolerability, PK, and biological activity of VT3989 administered, alone or in combination, once daily in 3- or 4-week cycles 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.
Intervention / Treatment
- Drug: VT3989
- Drug: Nivolumab & Ipilimumab
- Drug: Osimertinib
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 Expansion Cohorts 1 and 2: in mesothelioma cohorts, pathologically diagnosed advancedat a late stage, far along malignantcancerous, may grow and spread to other areas of the body 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.
- Part 2 Expansion Cohort 3: non-pleural mesothelioma patients with epithelioid histology, relapsed from or refractory to prior platinum-based chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells and immunotherapya treatment that uses a person's immune system to fight cancer.
- Part 2 Expansion Cohort 4: in the solid tumor cohort, pathologically diagnosed metastatic or locally advanced solid tumor with clearly inactivating NF2 mutations/alterations or YAP/TAZ gene rearrangements, which 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: pathologically diagnosed advanced malignant pleural mesothelioma with epithelioid histology, that has 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: pathologically diagnosed, metastatic or unresectable malignant mesothelioma including both pleural and non-pleural) patients who have not received systemic therapy.
- Part 3 Combination Cohort B: 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