A phase Ib/II, open-label, multicenter study of AEB071 and MEK162 in adult patients with metastatic uveal melanoma

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 12

Inclusion Criteria

1. Male or female patients >=18 years of age
2. Uveal (ocular) melanoma with biopsy-confirmed metastatic disease
3. Consent to a new tumor biopsy at baseline, Cycle 1 Day 15 (C1D15), and at disease progression
4. The presence of measurable disease according RECIST v1.1
5. WHO performance status of <=1

Exclusion Criteria

1. Any active metastatic CNS lesion
2. History of prior or current second malignancy (except adequately treated carcinoma of the cervix or localized basal cell carcinoma of the skin, or any other curatively treated malignancy that has not been treated or recurred in the past 3 years).
3. History or current evidence of retinal vein occlusion (RVO) in the contralateral eye, as assessed by ophthamologic examination at baseline or current risk factors for RVO.
4. Impaired cardiac function ro clinically significant cardiac disease; e.g. , LVEF < 50% as determined by MUGA scan or TTE
5. Serum creatinine of >1.5x ULN
6.Treatment with strong inducers or inhibitors (medications and herbal supplements) of cytochrome P450 3A4/5 (CYP3A4/5) or CYP3A4/5 substrates with a QT prolongation risk that cannot be discontinued at least 7 half lives (or if the half-life is unkonw, 14 days) prior to study drug treatment.
7.Prior exposure to a MEK or PKC inhibitor (i.e. patients treated in the Phase I will not be eligible for the Phase II)

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase 1b: Incidence of Dose Limiting Toxicities during the first cycle<br /><br>Phase II: Progression Free Survival (PFS)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Phase Ib/II: Adeverse events and serious adverse events, changes in laboratory<br /><br>values, and electrocardiograms. Dose interruptions, reductions and dose<br /><br>intensity.<br /><br>Phase 1b/11: Disease control Rate (DCR: CR(complete resonse)+PR (partial<br /><br>response) +SD (stable disease); Progression Free Survival (PFS); OS(overall<br /><br>survival); ORR (Overall Response Rate)<br /><br>Phase 1b: Concentration-time profiles of AEB071 and MEK162, PK parameters,<br /><br>including but not limited to AUC0-8h, Ctrough, Cmax, Tmax, accumulation ratio<br /><br>(Racc)</p><br>

Updated 4/19/2022