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 confirmeddiagnosis of advanced (unresectable or metastatic) mesothelioma or other solidtumors. Patients with solid tumors other than mesothelioma must have local availabledata for loss-of-function NF2/LATS1/LATS2 genetic alterations (truncating mutationor gene deletion; LATS1/LATS2 mutations will only be included in the dose escalationpart), or functional YAP/TAZ fusions. Patients with malignant EHE can be enrolledwith only histological confirmation of the disease. Patients must have failedavailable 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 differenttreatment groups: Group 1: Advanced (unresectable or metastatic) MPM patients who have failedavailable standard therapies for advanced/metastatic disease, be intolerant orineligible to receive such therapy, or for whom no standard therapy exists. Group 2: Advanced (unresectable or metastatic) solid tumor patients with availablelocal data for NF2 truncating mutation or deletions. Patient must have failedavailable 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 availablelocal data for functional YAP/TAZ fusions. EHE patients can be included with onlyhistological confirmation of the disease. Patient must have failed availablestandard therapies, be intolerant or ineligible to receive such therapy, or for whomno standard therapy exists. Group 4: Advanced (unresectable or metastatic) non-pleural mesothelioma patients whohave failed available standard therapies for advanced/metastatic disease, areintolerant or ineligible to receive such therapy, or for whom no standard therapyexists.

5. Presence of at least one measurable lesion according to mRECIST v1.1 formesothelioma patients, RECIST v1.1 for patients with other solid tumors, or RANO forpatients with primary brain tumors.

6. Patient must have a site of disease amenable to biopsy and be a candidate for tumorbiopsy according to the treating institution's guidelines. Patient must be willingto undergo a new tumor biopsy at screening/baseline, and again during therapy onthis study. An archival tumor sample may be used at screening. During the doseexpansion part of the study, a decision may be made to stop the collection ofon-treatment biopsies.

Exclusion Criteria:

1. Treatment with any of the following anti-cancer therapies prior to the first dose ofstudy treatment within the stated timeframes:

2. ≤ 4 weeks for thoracic radiotherapy to lung fields or limited field radiationfor palliation within ≤ 2 weeks prior to the first dose of study treatment. Anexception to this exists for patients who have received palliative radiotherapyto bone, who must have recovered from radiotherapy-related toxicities but forwhom a 2-week washout period is not required.

3. ≤ 4 weeks or ≤ 5 half-lives (whichever is shorter) for biological therapy (including monoclonal antibodies) or continuous or intermittent small moleculetherapeutics or any other investigational agent.

4. ≤3 weeks for treatment with cytotoxic agents or ≤ 6 weeks for cytotoxic agentswith risk of major delayed toxicities, such as nitrosoureas and mitomycin C.

5. ≤ 4 weeks for immuno-oncologic therapy, such as CTLA4, PD-1, or PD-L1antagonists

6. Prior treatment with TEAD inhibitor at any time

7. For mesothelioma patients: use of non-invasive antineoplastic therapy (e.g., tumortreating fields, brand name Optune LuaTM) within 2 weeks of the tumor assessment atscreening.

8. Malignant disease, other than that being treated in this study.

9. Insufficient renal function at Screening.

10. Clinically significant cardiac disease or risk factors at screening

11. Insufficient bone marrow function at screening.

12. Insufficient hepatic function at screening.

13. Patients who have the following laboratory values > Common Terminology Criteria forAdverse Events (CTCAE) grade 1:

14. Potassium

15. Magnesium

16. Total calcium (corrected for low serum albumin)

17. Known active COVID-19 infection.

18. Pregnant or nursing (lactating) women,

19. Japan only: patients with a history of drug- and/or non-drug-induced interstitiallung disease (ILD) ≥ Grade 2.

Other protocol-defined inclusion/exclusion criteria may apply.