Clinical Trial Finder

Inclusion Criteria:

• - Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol.

• - Patients must have NRAS mutation in codon 12, 13, 61 as determined via the MATCH Master Protocol.

• - Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically significant abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) - Creatinine =< 1.5 mg/dL, or calculated creatinine clearance (determined as per Cockcroft-Gault) >= 50mL/min.

• - Patients must have adequate cardiac function: - Left ventricular ejection fraction (LVEF) >= 50% as determined by a multigated acquisition (MUGA) scan or echocardiogram, - QTc interval =< 480 ms.

Exclusion Criteria:

• - Patients must not have known hypersensitivity to binimetinib or compounds of similar chemical or biologic composition.

• - Patients with melanoma are excluded.

• - Patients must not have any active central nervous system (CNS) lesion (i.e., those with radiographically unstable, symptomatic lesions) and/or leptomeningeal metastases.

• - NOTE: Patients treated with stereotactic radiotherapy or surgery are eligible if the patient remained without evidence of CNS disease progression >= 3 months.

Patients must be off corticosteroid therapy for >= 3 weeks.

• - Patients must not have a history or current evidence of retinal vein occlusion (RVO) or predisposing factors to RVO (e.g. uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes) - Patients must not have a history of retinal degenerative disease.

• - Patients must not have a history of Gilbert's syndrome.

• - Patients must not have uncontrolled arterial hypertension despite medical treatment.

• - Patients must not have active hepatitis B, and/or active hepatitis C infection.

- Patients must not have neuromuscular disorders that are associated with elevated creatine kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy) - Patients must not have impairment of gastrointestinal function or gastrointestinal disease (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) - Patients who have received prior MEK inhibitors are excluded

PRIMARY OBJECTIVE:

• I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

• I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

• II. To evaluate time until death or disease progression.

• III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

• IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE: Patients receive binimetinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Arms

Experimental: Treatment (binimetinib)

Patients receive binimetinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Interventions

Drug: - Binimetinib

Given PO