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

Novartis

Status and phase

Terminated

Phase 1

Conditions

Uveal Melanoma

Treatments

Drug: LXS196

Drug: LXS196 and HDM201

Study type

Interventional

Funder types

Industry

Identifiers

NCT02601378

CLXS196X2101

Details and patient eligibility

About

This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent and in combination with HDM201 in patients with metastatic uveal melanoma.

Enrollment

107 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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).