**Effective 07/22/21,  Please note that there are no available treatment assignment slots remain. 

Subprotocol M eligibility (in addition to master):
-Patients must have a TSC1 or TSC2 mutation as determined by the MATCH screening assessment
-Patients must not have uncontrolled diabetes mellitus
-Patients must not have had prior treatment with other known TORC1/2 inhibitors

**To clarify, the language in Section 2.1.9 of the EAY131-M Subprotocol should refer to "P450 (CYP) 3A4, CYP2C9 or CYP2C19," instead of duplicating CYP2C19 twice**

Subprotocol Q Eligibility (in addition to master):
-Patients’ tumor sample must have HER2 amplification > 7 based on targeted custom Ampliseq panel on the Ion Torrent PGM.
-Patients will be allowed if on anticoagulation (except warfarin and other coumarin derivatives) or on aspirin 81 mg by mouth daily. However, patients will not be allowed if on long acting anti-platelet agents such as clopidogrel.
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block).
-Patients must have ECHO/MUGA within 4 weeks prior to treatment assignment and must not have a left ventricular ejection fraction (LVEF) < 50% to be eligible.
-Patients with a diagnosis of Breast cancer or gastric/GEJ cancer will be excluded.
-Patients must not have known hypersensitivity to ado-trastuzumab emtansine or compounds of similar chemical or biologic composition.
-Patient must not have had any of the prior therapies: Trastuzumab, Pertuzumab, Ado-trastuzumab emtansine, Margetuximab, PF-05280014 (Pfizer, Trastuzumab Biosimilar), CT-P6 (Celltrion, Trastuzumab Biosimilar), ABP-980 (Amgen, Trastuzumab Biosimilar)

Subprotocol R Eligibility (in addition to master):
-Patients must have a BRAF non-V600 mutation or BRAF fusion as identified via the MATCH Master Protocol.
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have NONE of the following cardiac criteria:
--Clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block).
--Treatment-refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mmHg which cannot be controlled by anti-hypertensive therapy
-Patients with a history of interstitial lung disease or pneumonitis are excluded
-Patients must have an ECHO/MUGA within 4 weeks prior to treatment assignment and must not have a left ventricular ejection fraction (LVEF) < the institutional lower limit of normal (LLN).
-Patients must not have known hypersensitivity to trametinib or compounds of similar chemical or biologic composition or to dimethyl sulfoxide (DMSO).
-Patients must not have a history or current evidence/risk of retinal vein occlusion (RVO).
-Patients who previously received MEK inhibitors (including, but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623 and pimasertib) will be excluded.
-Patients who previously received monoclonal antibody therapy (eg. ipilimumab, nivolumab, pembrolizumab and others) must have stopped the prior therapy for 8 or more weeks before starting on trametinib. 

Subprotocol S1 eligibility (in addition to master eligibility):
-Patients must have deleterious inactivating mutations of NF-1 by the MATCH NGS assay.
-Patients who previously received MEK inhibitors (including, but not limited to, trametinib, binimetinib, cobimetinib, selumetinib, RO4987655 (CH4987655), GDC-0623 and pimarsertib) will be excluded.
-Patients who previously received monoclonal antibody therapy (eg. ipilimumab, nivolumab, pembrolizumab and others) must have stopped the prior therapy for 8 or more weeks before starting on trametinib.
-Patients with glioblastoma must have histologically or radiographically confirmed recurrent or progressive WHO Grade 4 glioma (glioblastoma).

Subprotocol U Eligibility (in addition to master):
-Patients must have a tumor that harbors an inactivating mutation in NF2. 
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block).
-Patients with known left ventricular dysfunction must have ECHO/MUGA within 4 weeks prior to treatment assignment and must not have left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible.
-Patients must not have known hypersensitivity to VS-6063 (defactinib) or compounds of similar chemical or biologic composition.
-Patients must not have a history of upper GI bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.
-Patients must not have prior treatment with a FAK inhibitor (eg. VS-6063 (defactinib) or GSK2256098) and must not be participating or have participated in the COMMAND trial of maintenance therapy of VS-6063 (defactinib) vs. placebo, for mesothelioma.

Subprotocol V Eligibility (in addition to master):
-Patients must have a somatic cKIT mutation in exon 9, 11, 13 or 14, excluding exon 17 or 18 mutations.
-Serum calcium must be less than or equal to 12.0 mg/dL
-Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block)
-Patients must have an ECHO/MUGA within 4 weeks prior to treatment assignment and must not have a left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN).
-Patients must not have known hypersensitivity or excess toxicity from sunitinib or compounds of similar chemical composition or biologic effect.
-Patients must not have had prior therapy with sunitinib.
-Patients must not have GIST, renal cell carcinoma, or pancreatic neuroendocrine tumor
-Patients must not have pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
-Patients may not have a major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to starting sunitinib.
-Patients with known brain metastases should be excluded
-Patients who require therapeutic doses of coumarin derivative anticoagulants such as warfarin are excluded, although doses up to 2 mg daily are permitted for prophylaxis of thrombosis. Note: Low molecular weight heparin is permitted provided that the patient’s PT INR is < 1.5