Pharmacokinetic Drug-drug Interaction Study of Encorafenib and Binimetinib on Probe Drugs in Patients With BRAF V600-mutant Melanoma or Other Advanced Solid Tumors

Key Inclusion Criteria - Patients must meet all of the inclusion criteria to be eligible
for enrollment into the study:

- Histologically confirmed diagnosis of locally advanced, unresectable or metastatic
cutaneous melanoma or unknown primary melanoma American Joint Committee on Cancer
(AJCC) Stage IIIB, IIIC or IV; or other BRAF V600-mutant advanced solid tumors

- Presence of BRAF V600E and/or V600K mutation in tumor tissue prior to enrollment, as
determined using a local test;

- Evidence of measurable or non-measurable lesions

- Patient with unresectable locally advanced or metastatic melanoma who has received no
prior treatment or progressed on or after prior systemic therapy; Note: Prior therapy
with a BRAF proto-oncogene serine-threonine protein kinase (BRAF) inhibitor and/or a
mitogen-activated protein (MAP) kinase (MEK) inhibitor is permitted except in the
regimen immediately prior to study entry

- Patient with other (non-melanoma) BRAF V600E and/or V600K -mutant advanced solid
tumors who has progressed on standard therapy or for whom there are no available
standard therapies; Note: Prior therapy with a BRAF inhibitor and/or a MEK inhibitor
is permitted except in the regimen immediately prior to study entry

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

- Adequate bone marrow, hepatic and renal function as specified in the protocol

- ARM 1 ONLY: Non-smoker who has not used nicotine containing products for at least 3
months prior to the first dose.

Key Exclusion Criteria - Patients meeting any of the following criteria are not eligible
for enrollment in the study:

- Symptomatic brain metastasis. Patients previously treated or untreated for these
conditions that are asymptomatic in the absence of corticosteroid and anti-epileptic
therapy are allowed. Brain metastases must be stable, with imaging (e.g., magnetic
resonance imaging [MRI] or computed tomography [CT] demonstrating no current evidence
of progressive brain metastases at screening);

- Symptomatic or untreated leptomeningeal disease;

- History or current evidence of retinal vein occlusion (RVO) or current risk factors
for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity
or hypercoagulability syndromes);

- Clinically significant cardiac disease

- Known hyper-coagulability risks other than malignancy (e.g., Factor V Leiden
syndrome);

- Thromboembolic event except catheter-related venous thrombosis ≤ 12 weeks prior to
starting study treatment.

- Discontinuation of prior BRAF and/or MEK inhibitor treatment due to left ventricular
dysfunction, pneumonitis/interstitial lung disease, or retinal vein occlusion;

- ARM 1 ONLY: Positive urine cotinine test at screening

- ARM 3 ONLY:

- History of psychosis, depression or mania;

- History of angioedema;

- History of mitral valve prolapse;

- History of left ventricular hypertrophy;