Ensartinib in Treating Patients with Advanced Melanoma Harboring ALK Alterations

Inclusion Criteria

• Histologically confirmed advanced malignant melanoma, regardless of subtype (for screening and treatment phases)
• Progression following PD-1 based checkpoint inhibitor therapy, with or without ipilimumab; tumors harboring BRAF V600 alterations must also have received prior therapy with BRAF inhibitors (with or without a MEK inhibitor) (for treatment phase); patients with uveal melanoma are exempt from PD-1 based progression since there is no accepted standard frontline therapy
• Tumors must harbor an alteration in ALK using a CLIA-certified laboratory, including, but not limited to, ALK^ATI, ALK fusions, or ALK mutations (for treatment phase)
• Disease must be measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1; disease that has undergone local therapy in the past 30 days is not considered measurable unless the investigator has documented progression despite the local therapy * If a patient has consented to the pre-screening portion, has been determined to have ALK alterations, but has no measurable disease, the trial may be favored later, and the patient should be consented (or re-consented) to the treatment portion of the trial at the discretion of the investigator (for treatment phase)
• Asymptomatic untreated brain metastases are allowed; symptomatic metastases that have undergone local therapy with radiation therapy (RT) or surgery and have not required an increase in steroid dose in prior 2 weeks are allowed; disease that has undergone local therapy is not considered measurable (for treatment phase)
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2 (for treatment phase)
• Total bilirubin =< 1.5 x upper limit of normal (ULN); patients with Gilbert’s Syndrome must have bilirubin =< 3 x ULN (for treatment phase)
• Aspartate aminotransferase (AST / serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT / serum glutamic pyruvic transaminase [SGPT]) =< 3 x ULN (=< 5 x if liver metastases are present) (for treatment phase)
• Estimated glomerular filtration rate (GFR) >= 30 mL/min using a cancer-specific GFR model (for treatment phase)
• Hemoglobin >= 9 g/dL (for treatment phase)
• Neutrophils >= 1.5 x 10^9/L (for treatment phase)
• Platelets >= 100 x 10^9/L (for treatment phase)
• Patients must agree to use effective means of contraception (for treatment phase)

Exclusion Criteria

• Any prior ALK inhibition (for screening and treatment phases)
• Prior therapy with immune-activating agents within less than 1 cycle length prior to first day of study treatment (e.g. 3 weeks for ipilimumab or pembrolizumab; 2 weeks for nivolumab) (for treatment phase)
• Any other systemic or regional anticancer therapy (cytotoxic chemotherapy, embolization) within 3 weeks or 1 cycle length, whichever is shorter, prior to first day of study treatment (for treatment phase)
• Prior RT or clinically relevant major surgery (e.g. craniotomy, metastasectomy) within 2 weeks prior to first day of study treatment (for treatment phase)
• Any other active malignancy other than melanoma that, in the opinion of the investigator, would interfere with study participation (for treatment phase)
• Receipt of any other systemic anticancer therapy except for hormonal therapy for a hormonally sensitive (e.g. breast or prostate) cancer and BRAF inhibitors (with or without a MEK inhibitor) (for treatment phase)
• Receipt of strong CYP3A inhibitors or inducers (for treatment phase)
• Clinically significant cardiovascular disease, including: * Corrected QT (QTc) interval by Bazett’s formula > 480 ms (for treatment phase) * Symptomatic bradycardia < 45 beats per minute (for treatment phase) * Other clinically significant electrocardiogram (ECG) abnormalities (e.g. bundle branch block) may be eligible after discussion with the principal investigator (for treatment phase) * Clinically uncontrolled hypertension in the investigator’s opinion (for treatment phase) * The following within 6 months prior to cycle 1 day 1: ** Congestive heart failure (New York Heart class III or IV) (for treatment phase) ** Cardiomyopathy (for treatment phase) ** Arrhythmia or conduction abnormality requiring medication; note: patients with atrial fibrillation/flutter adequately controlled by medication in the opinion of the treating physician and arrhythmias controlled by pacemakers are eligible (for treatment phase) ** Severe / unstable angina, coronary artery/peripheral bypass graft, or myocardial infarction (for treatment phase) ** Cerebrovascular accident or transient ischemia (for treatment phase)
• Any serious, active infection at the time of treatment such as bacteremia (for treatment phase)
• Interstitial lung disease or pneumonitis that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity; patients with prior pneumonitis that has resolved are eligible (for treatment phase)
• Patients must not be pregnant or breast feeding, or unable or unwilling to use proper contraception during the study and up to 3 months following study completion (for treatment phase)