CLXS196X2101 (Novartis)

Leids Universitair Medisch Centrum

| A Phase I, multi-center, open-label, study of LXS196, an oral protein kinase C inhibitor, in patients with metastatic uveal melanoma EUDRACT number 2015-002158-11 The purpose of this study is to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent in patients with metastatic uveal melanoma. LXS196 is a potent, orally bioavailable, selective inhibitor of the PKC family of kinases. In pre-clinical uveal melanoma efficacy models, LXS196 dosed as a single agent leads to tumor regression at doses below its maximum tolerated dose (MTD). LXS196 therefore provides the opportunity to treat uveal melanoma patients with a potent, PKC selective therapy that targets one of the key downstream signaling pathways from the GNAQ/GNA11 mutations that characterize this disease.

fase 1/II studie met LXS96


Belangrijkste in/exclusiecriteria:
| Male or female patients ≥18 years of age • ● Metastatic histologically or cytologically confirmed uveal melanoma with • pathologic confirmation that is judged to be progressive in the opinion of the • treating physician. • ● 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. Exceptions are described in Section 5.2. ● Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression. Treated brain metastases must have been stable for at least 1 month. ● Impaired cardiac function or clinically significant cardiac diseases listed in Section 5.2. ● 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 ● 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) ≤ 1.0 x 109/L (1000/mm3). ● Platelets ≤ 75 x 109/L (75,000/mm3). ● Hemoglobin (Hgb) ≤ 90 g/L (9 g/dL).

Dr. H.W. Kapiteijn, internist-oncoloog, LUMC

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