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

This is an interventional treatment trial for Uveal Melanoma focused on measuring Uveal melanoma, Metastatic uveal melanoma, Phase I, LXS196, PKC inhibitor, HDM201, HDM2 inhibitor, dose escalation Read More

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).