MEK and Autophagy Inhibition in Metastatic/Locally Advanced, Unresectable Neuroblastoma RAS (NRAS) Melanoma

Exclusion Criteria

• •1. Prior to the first dose of study treatment patient who received systemic antineoplastic therapy (including unconjugated therapeutic antibodies and toxin immunoconjugates) or any investigational therapy within 4 weeks (6 weeks for nitrosurea or mitomycin-C, antibodies like ipilimumab, pembrolizumab and nivolumab) or within 7-half lives of the investigational therapy prior to starting study treatment, whichever is longer.
• •2. Patient received radiotherapy within 2 weeks prior to the first dose of study treatment except localized radiation therapy for symptomatic bone metastasis
• •3. Patients with multiple primary malignancies may be enrolled if nonmelanoma tumor(s) are determined stable by treating investigator and do not require active treatment.
• •4. Patients with symptomatic brain metastases or cranial epidural disease. Asymptomatic patients with brain metastases can be included.
• •5. Has retinal degenerative disease (hereditary retinal degeneration or age-related macular degeneration), history of uveitis, or history of Retinal Vein Occlusion (RVO) or any eye condition that would be considered a risk factor for RVO (e.g., uncontrolled glaucoma or ocular hypertension).
• •6. Current evidence of uncontrolled, significant intercurrent illness including, but not limited to, the following conditions:
• •* Cardio-vascular disorders: Congestive heart failure New York Heart Association (NYHA) class 3 or 4, unstable angina, uncontrolled cardiac arrhythmias, uncontrolled hypertension. Stroke, myocardial infarction or other ischemic event within 6 months before first dose.
• •* History of Glucose-6-Phosphate dehydrogenase (G6PD) deficiency
• •* Patients who have neuromuscular disorders that are associated with elevated Creatine Kinase (CK)
• •* Impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection that under the judgement of the Principal Investigator (PI) may impair absorption of study drugs)
• •* Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
• •7. Known positive serology for Human Immunodeficiency Virus (HIV), active Hepatitis B, and/or active Hepatitis C infection.
• •8. Patients who have undergone major surgery ≤ 3 weeks prior to starting study drug or who have not recovered from side effects of such procedure.
• •9. 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 Human chorionic gonadotropin (hCG) laboratory test.
• •10. Medical, psychiatric, cognitive or other conditions that may compromise the patient's ability to understand the patient information, give informed consent, comply with the study protocol or complete the study
• •11. Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 Grade≥3)