A Phase I Study of LXS196 in Patients With Metastatic Uveal Melanoma.

Key Inclusion Criteria:

* Male or female patients ≥18 years of age
* Diagnosis of uveal melanoma with histological or cytological confirmed metastatic disease. Disease must be treatment naive or have progressed (radiologically or clinically) on most recent therapy.
* Willingness to provide newly obtained tumor tissue at baseline and on treatment unless contraindicated by medical risk in the opinion of the treating physician.
* Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \> 20 mm with conventional techniques or as \>10 mm with CT scan.
* ECOG performance status ≤ 1

Key Exclusion Criteria:

* Malignant disease other than that being treated in this study.
* Symptomatic or untreated CNS metastases or spinal cord compression. Brain metastasis must be stable with verification by imaging .
* Impaired cardiac function or clinically significant cardiac diseases
* History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism (applicable to combination part only).
* Patients who are receiving treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following:
* known and possible risk for QT prolongation
* known to be strong inducers or inhibitors of CYP3A4/5 (for single agent part); known to be moderate to strong inducers or inhibitors of CYP3A4/5 (for combination part)
* known to be inducers or inhibitors of P-gp
* known to be substrates of CYP3A4/5 and P-gp with a narrow therapeutic index
* Patients with abnormal laboratory values, defined as any of the following:
* AST or ALT \> 3 times ULN, AST or ALT \> 5 times ULN for patients with liver metastases.
* Total bilirubin \> 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin \> 3.0 x ULN or direct bilirubin \> 1.5 x ULN.
* Absolute neutrophil count (ANC) ≤ 1.5 x109/L.
* Platelets ≤ 100 x 109/L.
* Hemoglobin (Hgb) ≤ 90 g/L (9 g/dL).
* Creatinine \> 1.5 x ULN
* Patients receiving live vaccines due to the expected bone marrow toxicity (applicable to combination part only).
* Patients treated with growth factors targeting the myeloid lineage (e.g. G-CSF, GM-CSF and M-CSF) within 2 weeks of starting study treatment. (applicable to combination part only).