A Phase I, Multicenter, Open-label, Dose-escalation Study of Oral LGX818 in Adult Patients With Locally Advanced or Metastatic BRAF Mutant Melanoma
For the dose escalation phase:
1. Histologically confirmed diagnosis of locally advanced or metastatic melanoma (stage
IIIB to IV per American Joint Committee on Cancer [AJCC]). For the dose expansion
phase: (i) Histologically confirmed diagnosis of locally advanced or metastatic
melanoma (stage IIIB to IV per American Joint Committee on Cancer [AJCC]), or (ii)
confirmed diagnosis and non-resectable advanced metastatic colorectal cancer (mCRC)
for which no further effective standard therapy exists.
2. Written documentation of BRAF V600E mutation, or any other BRAF V600 mutation.
3. Evidence of measurable disease
1. Previous therapy with a MEK inhibitor.
2. Symptomatic or untreated leptomeningeal disease.
3. Symptomatic or untreated brain metastasis.Patients previously treated for these
conditions that are asymptomatic in the absence of corticosteroid therapy are allowed
to enroll. Brain metastasis must be stable with verification by imaging.
4. Known acute or chronic pancreatitis.
5. Clinically significant cardiac disease
6. Impairment of gastrointestinal (GI) function or GI disease that may significantly
alter the absorption of oral LGX818
7. Previous or concurrent malignancy. Exceptions to this exclusion criteria include:
adequately treated basal cell or squamous cell skin cancer; in situ carcinoma of the
cervix, treated curatively and without evidence of recurrence for at least 3 years
prior to study entry; or other solid tumor treated curatively, and without evidence
of recurrence for at least 3 years prior to study entry.
8. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a
female after conception and until the termination of gestation, confirmed by a
positive hCG laboratory test (> 5 mIU/mL).
9. History of thromboembolic or cerebrovascular events within the last 6 months
Other protocol-defined inclusion/exclusion criteria may apply