Testing Trametinib as a Potential Targeted Treatment in Cancers With NF1 Genetic Changes (MATCH-Subprotocol S1)

Inclusion Criteria:

• Patients must have met applicable eligibility criteria in the Master MATCH Protocolprior to registration to treatment subprotocol

• Patients must have deleterious inactivating mutations of NF-1, or anotheraberration, as determined via the MATCH Master Protocol

• Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatmentassignment and must have NONE of the following cardiac criteria:

• Clinically important abnormalities in rhythm, conduction or morphology ofresting ECG (e.g. complete left bundle branch block, third degree heart block).

• Treatment-refractory hypertension defined as a blood pressure of systolic > 140mmHg and/or diastolic > 90 mmHg which cannot be controlled by anti-hypertensivetherapy

• Patients must have an echocardiogram (ECHO) or a nuclear study (multigatedacquisition scan [MUGA] or First Pass) within 4 weeks prior to registration totreatment and must not have a left ventricular ejection fraction (LVEF) < theinstitutional lower limit of normal (LLN). If the LLN is not defined at a site, theLVEF must be > 50% for the patient to be eligible

• Patients who previously received monoclonal antibody therapy (eg. ipilimumab,nivolumab, pembrolizumab and others) must have stopped the prior therapy for 8 ormore weeks before starting on trametinib

• Patients with glioblastoma must have histologically or radiographically confirmedrecurrent or progressive World Health Organization (WHO) grade 4 glioma (glioblastoma)

• NOTE: All baseline and post-baseline disease assessments must be performedusing contrast-enhanced cranial magnetic resonance spectroscopy (MRI) orcontrast-enhanced computed tomography (CT) for subjects who cannot have MRIperformed

Exclusion Criteria:

• Patients with a history of interstitial lung disease or pneumonitis are excluded

• Patients must not have known hypersensitivity to trametinib or compounds of similarchemical or biologic composition or to dimethyl sulfoxide (DMSO).

• Patients must not have a history or current evidence/risk of retinal vein occlusion (RVO). An eye exam is required at baseline

• Patients who previously received MEK inhibitors (including, but not limited to,trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623and pimasertib) will be excluded