Study of Ceritinib in Patients With Unresectable Melanoma

Ceritinib is a pill that has been approved for patients with metastatic non-small cell lung
cancer (NSCLC) by the US Food and Drug Administration (FDA). While ceritinib is not currently
FDA-approved specifically in melanoma, researchers believe ceritinib may also help keep
melanoma cancer cells from growing and therefore potentially help patients with melanoma as
well. Therefore, the aim of this study is to determine how effective ceritinib is in patients
with advanced melanoma.

Inclusion Criteria:

- Diagnosis of advanced/unresectable melanoma (AJCC v.8 Stage 3C/D/4)

- Measurable disease, defined as per Response Evaluation Criteria in Solid Tumors
(RECIST) 1.1

- Must have at least one tumor site accessible for a biopsy

- Documented disease refractory to at least one PD1/PD-L1 (+/- CTLA-4) inhibitor
treatment, or intolerance to these drugs

- If BRAFV600-mutant, refractory disease to at least one BRAF inhibitor and a MEK
inhibitor (defined as progression while on treatment), or intolerance to these drugs

- Prior treatment-related toxicity resolved to ≤ Grade 2 or baseline

- Prior radiation allowed

- Eastern Cooperative Oncology Group (ECOG) performance status ≤2

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and for
the duration of study participation and for 90 days after completion of ceritinib
administration.

- Participants must have normal organ and marrow function.

Exclusion Criteria:

- Potential participants with known hypersensitivity to any of the excipients of
ceritinib (microcrystalline cellulose, mannitol, crospovidone, colloidal silicon
dioxide and magnesium stearate).

- An untreated or uncontrolled brain metastases or evidence of leptomeningeal disease.
Patients with asymptomatic brain metastases or previously treated brain metastases
that are stable (i.e., not requiring corticosteroids) at the time of study start will
be eligible.

- Previous malignancy is not an exclusion provided that the other malignancy is
considered under control, patient is not on concomitant anti-cancer drug therapy, and
target lesions from melanoma are clearly defined for response assessment.

- Other severe, acute, or chronic medical conditions including uncontrolled diabetes
mellitus or psychiatric conditions or laboratory abnormalities that, in the opinion of
the investigator, may increase the risk associated with study participation or may
interfere with the interpretation of study results.

- Clinically significant, uncontrolled heart disease and/or recent cardiac event (within
6 months), such as:

1. unstable angina within 6 months prior to screening;

2. myocardial infarction within 6 months prior to screening;

3. history of documented congestive heart failure (New York Heart Association
functional classification III-IV);

4. cardiac arrhythmias not controlled with medication;

5. Corrected QT (QTcF) >470 ms at baseline

- A history of interstitial lung disease or interstitial pneumonitis, including
clinically significant radiation pneumonitis (i.e., affecting activities of daily
living or requiring therapeutic intervention). (Note, this does NOT include
immune-mediated pneumonitis)

- A history of pancreatitis

- Impaired gastrointestinal (GI) function or GI disease that may alter absorption of
ceritinib or inability to swallow

- Receiving medications that meet one of the following criteria and that cannot be
discontinued at least 1 week prior to start of treatment with ceritinib and for the
duration of participation:

1. Medication with a known risk of prolonging the QT interval or inducing Torsades
de Pointes

2. Strong inhibitors or strong inducers of CYP3A4/5, and Medications with a low
therapeutic index that are primarily metabolized by CYP3A4/5, and/or CYP2C9

3. Therapeutic doses of warfarin sodium (Coumadin) or any other coumadin-derived
anti-coagulant. Anticoagulants not derived from warfarin are allowed (e.g.,
dabigatran, rivaroxaban, apixaban).

4. Unstable or increasing doses of corticosteroids in the 5 days before first dose
of study treatment.

5. Enzyme-inducing anticonvulsive agents