• Age 16 or greater
• Histologically or cytologically confirmed Stage IV CRC
• Must contain a BRAF V600E mutation on local (FMI or Caris) or central testing
• No prior systemic treatment in metastatic setting
• Prior adjuvant or neoadjuvant therapy is OK only if relapse/metastasis is 6 months or greater from the end of the neo/adjuvant treatment
• No history of acute or chronic pancreatitis
• No symptomatic brain mets
• Must have measurable disease

• Histologically confirmed EC including: endometrioid, serous, undifferentiated, and carcinomsarcoma
• TP53 WT assessed by NGS via central vendor
• Completed a single line, at least 12 weeks, of platinum-based therapy (not including adjuvant or neoadjuvant tx for Stage 1-II disease) adn achieved confirmed PR or CR by RECIST.
• If Primary Stage IV, may have had surgery or not. If surgery, must have had R0 or R1 resection
• Must be able to initiate study drug 3-8 weeks following completion of final dose of chemo
• ECOG PS 0-1
• No uterine sarcoma
• No concurrent systemic steroid therapy above 10mg prednisone or equivalent
• No previous treatment with an XPO1 inhibitor
• No active brain mets

• Histologic confirmed diagnosis of GBM per WHO classification criteria
• Age >or= 22
• Recovered from maximal debulking surgery, if applicable (gross total resection, partial resection, and biopsy-only patients are all acceptable)
• Planned treatment with RT-TMZ followed by TTFields and maintenance TMZ
• KPS >or= 70%
• Must have stable or decreasing steroid use
• Concomitant RT with TMZ planned to start no later than 8 weeks post surgery
• Able to undergo MRI with contrast of brain
• No infratentorial or leptomeningeal disease
• No plts <100, ANC <1.5, AST/ALT > 3xULN, Tbili >1.5x ULN, creatinine >1.7
• No institutionalized patients
• No active implanted medical devices, bullet fragments, or other skull defects

• Malignant solid tumor with pathogenic inactivating TSC1 or TSC2 alterations. GEnetic alterations should be identified using NGS in tumor tissue or liquid biopsy
• Metastatic or locally advanced solid tumors
• Must have received all standard therapies appropriate for their tumor type and stage of disease or, in the opinion of the investigator, the patient would b e unlikely to tolerate or derive clinically meaningful benefit from appropriate SOC therapy
• Measurable disease
• ECOG PS 0-1
• Fasting tryglecerid must be < or = 300; fast serus cholesterol must be < or = to 350
• No prior treatment with MTOR inhibitor
• No primary brain tumors
• No known HIV

CURRENTLY ONLY THE MELANOMA COHORT IS ENROLLING

Inclusion Criteria:

1. Histologically or cytologically-documented solid tumors.
2. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
3. Demonstrate adequate organ function.

Exclusion Criteria:

1. Prior history of or active malignant disease other than that being treated in this study.
2. Known brain metastases or cranial epidural disease.
3. A known hypersensitivity to the components of the study therapy or its' analogs.