A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors

Inclusion Criteria

• •1. Signed informed consent must be obtained prior to participation in the study.
• •2. Male or female patients must be ≥ 18 years of age.
• •3. Dose escalation part: patients with histologically or cytologically confirmed diagnosis of advanced (unresectable or metastatic) mesothelioma or other solid tumors. Patients with solid tumors other than mesothelioma must have local available data for loss-of-function NF2/LATS1/LATS2 genetic alterations (truncating mutation or gene deletion; LATS1/LATS2 mutations will only be included in the dose escalation part), or functional YAP/TAZ fusions. Patients with malignant EHE can be enrolled with only histological confirmation of the disease. Patients must have failed available standard therapies, be intolerant of or ineligible for standard therapy, or for whom no standard therapy exists.
• •4. Dose expansion part: the following patients will be enrolled into 3 different treatment groups:
• •Group 1: Advanced (unresectable or metastatic) MPM patients who have failed available standard therapies for advanced/metastatic disease, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists.
• •Group 2: Advanced (unresectable or metastatic) solid tumor patients with available local data for NF2 truncating mutation or deletions. Patient must have failed available standard therapies, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists.
• •Group 3: Advanced (unresectable or metastatic) solid tumor patients with available local data for functional YAP/TAZ fusions. EHE patients can be included with only histological confirmation of the disease. Patient must have failed available standard therapies, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists.
• •Group 4: Advanced (unresectable or metastatic) non-pleural mesothelioma patients who have failed available standard therapies for advanced/metastatic disease, are intolerant or ineligible to receive such therapy, or for whom no standard therapy exists.
• •5. Presence of at least one measurable lesion according to mRECIST v1.1 for mesothelioma patients, RECIST v1.1 for patients with other solid tumors, or RANO for patients with primary brain tumors.
• •6. Patient must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening/baseline, and again during therapy on this study. An archival tumor sample may be used at screening. During the dose expansion part of the study, a decision may be made to stop the collection of on-treatment biopsies.