7 copy numbers by NGS as determined by the MATCH screening assessment.
-Patients must not have breast cancer, gastric/GEJ/esophageal adenocarcinoma or mixed histology, or gastric/GEJ NOS tumors.
-Patients must not have received prior anti-HER2 therapies, including trastuzumab, pertuzumab, T-DM1, lapatinib, afatinib, neratinib, dacomitinib, canertinib.

- Patients with a history of Hyperphosphatemia will be excluded.
-Patients may not have received strong inhibitors or potent inducers of CYP3A within 2 weeks before the first dose of study treatment. Patients with inability to discontinue treatment with a strong CYP3A4 and/or CYP2C9 inhibitor or inducer prior to start of treatment are excluded.
-Patients who have previously received treatment with a FGFR-targeted inhibitor are excluded. Such inhibitors include AZD4547, BGJ398, BAY1163877 and LY2874455). Prior non-selective FGFR inhibitor treatment (e.g. Pazopanib, dovitinib, ponatinib, brivanib, lucitanib, lenvatinib) are allowed.
-Patients must not have any history of or current evidence of renal or endocrine alterations of calcium/phosphate homeostasis, or history of or current evidence of extensive tissue calcification (by evaluation of the clinician), including but not limited to, the soft tissue, kidneys, intestine, myocardium and lung with the exception of calcified lymph nodes and asymptomatic vascular calcification per investigators’ judgment.
-Patients with transitional cell carcinoma of the bladder and /or urothelial tract are not eligible. These patients are encouraged to enroll in the ongoing disease-specific studies.
-Patients with impaired renal function (glomerular filtration rate [GFR] 60 mL/min) are excluded. GFR should be assessed by direct measurement (i.e., creatinine clearance or ethyldediaminetetra-acetate) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula).
-Patients with persistent phosphate level > ULN during screening (within 14 days of treatment and prior to Cycle 1 Day 1) and despite medical management are excluded.
-Patients with a history of or current uncontrolled cardiovascular disease as stated below are excluded
-Patients with impaired wound healing capacity defined as skin/decubitus ulcers, chronic leg ulcers, known gastric ulcers, or unhealed incisions are excluded.

-Patients must fulfill all eligibility criteria outlined in Section 3.1 of MATCH Master Protocol (excluding Section 3.1.6) at the time of registration to treatment step (Step 1, 3, 5, 7).
-Patients must have FGFR Mutation or Fusion as determined via the MATCH Master Protocol and as described in Appendix II
-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
-Patients must not have known hypersensitivity to JNJ-42756493 (erdafitinib) or compounds of similar chemical or biologic composition.
-Patients with current evidence of corneal or retinal disorder/keratopathy are excluded.
-Patients must not be currently using medications that can elevate serum phosphorous and/or calcium levels.
-Patients with a history of hyperphosphatemia will be excluded.
-Patients may not have received strong inhibitors or potent inducers of CYP3A within 2 weeks before the first dose of study treatment. Patients with inability to discontinue treatment with a strong CYP3A4 and/or CYP2C9 inhibitor or inducer prior to start of treatment are excluded.
-Patients who have previously received treatment with a FGFR-targeted inhibitor are excluded. Such inhibitors include AZD4547, BGJ398, BAY1163877 and LY2874455). Prior non-selective FGFR inhibitor treatment (e.g. Pazopanib, dovitinib, ponatinib, brivanib, lucitanib, lenvatinib) are allowed.

-Patients must not have had prior treatment with other known TORC1/2 inhibitors

**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).