Oral TEAD Inhibitor Targeting the Hippo Pathway in Subjects with Advanced Solid Tumors

Inclusion Criteria:

1. Signed informed consent must be obtained prior to participation in the study.

2. Male or female subjects ≥ 18 years of age.

3. If feasible, subjects must be willing to consent to the submission of formalin-fixedparaffin-embedded tissue blocks or slides of tumor tissue, preferably frompre-treatment, baseline fresh tumor biopsy at Screening. Alternatively, archivaltumor FFPE blocks or, unstained slides of tumor tissue from available archivalsources are acceptable.

4. In the dose escalation cohort: Subjects with histologically proven advanced,unresectable, locally recurrent, or metastatic malignancy that has progressed on orfollowing standard-of-care therapies and for whom there is no available therapyknown to confer clinical benefit, regardless of the presence or absence of NF2deficiency or other genetic alterations of the Hippo pathway. Subjects withhistological confirmation of MPM; subjects with NF2-deficient MPM determined bylocal test results for testing can also be enrolled as well as subjects with anyother solid tumors with documented NF2 deficiency determined by local test resultsfor testing, including, but not limited to, meningioma, cholangiocarcinoma, thymoma,mucoepidermoid NSCLC, HCC, and others. Subjects diagnosed with EHE with documentedTAZ-CAMTA1 or YAP1-TFE3 gene fusions, as determined by local tests and subjects withsolid tumors who have YAP1/TAZ gene fusions as determined by local test results canalso be enrolled in the dose escalation part of the study.

5. In the Dose expansion: Four groups of subjects will be enrolled:

6. Cohort 1: Subjects with histological confirmed MPM and that have documented NF2deficiency,

7. Cohort 2: Subjects with other documented NF2-deficient solid tumors agnostic totumor type including, but not limited to, meningioma, cholangiocarcinoma,thymoma, NSCLC, HCC, and others.

8. Cohort 3: Subjects with histopathological diagnosis of epithelioidhemangioendothelioma (EHE) and documented TAZ-CAMTA1 or YAP1-TFE3 gene fusions,as determined by local test results. Subjects who have objective diseaseprogression to prior therapy or have active disease and cancer-related painrequiring narcotics for management are eligible.

9. Cohort 4: Subjects with any solid tumor with documented YAP1/TAZ gene fusionsas determined by local test results.

10. In the Osimertinib Combination Cohort subjects must have a histologically proven,incurable, locally advanced or metastatic NSCLC expressing osimertinib-sensitiveEGFR mutations; have evidence of radiological disease progression on prior receiptof Osimertinib and have progressed on additional anticancer therapy such aschemotherapy.

11. Subjects can have measurable or evaluable disease by RECIST 1.1 criteria as assessedby the Investigator/local radiologist.

Exclusion Criteria:

1. Subjects with untreated or symptomatic primary central nervous system (CNS) tumorsor with intracranial metastases (excluding primary CNS tumors that may be eligiblefor enrollment as part of Cohort 2 e.g., NF-2 deficient meningioma) a. Subjects with leptomeningeal metastases are excluded

2. Uncontrolled or life-threatening symptomatic concomitant disease

3. Clinically significant cardiovascular disease as defined in the protocol

4. Women who are pregnant or breastfeeding

5. Subjects who are unable to swallow or retain oral medication

6. Prior treatment/exposure to YAP/TAZ/TEAD inhibitors

7. Other inclusion/exclusion criteria may apply