A Phase 1, Open-Label, Dose Escalation and Dose Expansion Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of Orally Administered CB-5083 in Subjects With Advanced Solid Tumors

• Males and females ≥18 years of age;

• Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1

• Acceptable bone marrow and organ function at screening as described below:

∙ ANC ≥ 1,500/µL;

‣ Platelet count ≥ 100,000/µL;

‣ Total bilirubin ≤ 1.5 × ULN or ≤ 3.0 × ULN for subjects with hereditary benign hyperbilirubinemia;

‣ AST (SGOT) ≤ 3 × ULN (≤ 5 × ULN if liver metastases are present);

‣ ALT (SGPT) ≤ 3 × ULN (≤ 5 × ULN if liver metastases are present);

‣ Serum creatinine ≤ 1.5 mg/dL or a measured creatinine clearance ³ 60 mL/min according to Cockcroft-Gault formula

• Left ventricular ejection fraction informed (LVEF) ≥ 55%;

• Ability to swallow and retain oral medications;

• Negative serum beta-human Chorionic Gonadotropin (β-hCG) test in women of childbearing potential (WOCBP); Note, subject must agree to use dual barrier contraceptive methods; and

• Willing and able to provide written informed consent and comply with the requirements of the study;

• Phase 1a Dose Escalation only - Histologically confirmed advanced solid tumor for which standard therapy does not exist or is no longer effective

• Food Effect Stage - willing and able to ingest a standard meal

⁃ Phase 1b All Expansion Cohorts - Evidence of measurable disease per RECIST, v1.1. Measurable disease is defined as a lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded) with a minimum size of 10 mm by computed tomography (CT) scan;

⁃ Phase 1b All Expansion Cohorts - Prior treatment with embolization or ablative therapies is allowed if measurable disease remains outside of the treated area or if there is definitive progression in the treated lesions. There is no limit on the number of prior procedures;

⁃ Phase 1b Dose Expansion RAS Mutated mCRC Arm only - Histologically confirmed colorectal cancer with a K-RAS or N-RAS mutation in exons 2,3 and 4 that is metastatic or unresectable;

⁃ Phase 1b Dose Expansion RAS Mutated mCRC Arm only - At least 2 prior systemic therapies for the treatment of metastatic colorectal cancer. Neo-adjuvant and adjuvant therapies may not be counted as part of the prior therapy requirements. At least 7 subjects should be naïve to treatment with regorafenib;

⁃ Phase 1b Optional Dose Expansion Advanced RCC Arm only - Histologically confirmed metastatic renal cell carcinoma;

⁃ Phase 1b Optional Dose Expansion Advanced RCC Arm only - Must have received 2 prior therapies for metastatic RCC, including a vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI) and an immune checkpoint inhibitor (ie anti-PD-1) (if approved and available for commercial use in the local country). At least 7 subjects should be naïve to treatment with prior inhibitors of mammalian target of rapamycin (mTOR) (eg. everolimus);

⁃ Phase 1b Optional Dose Expansion pNET Arm only - Histologically confirmed low-grade or intermediate-grade, unresectable or metastatic pNET tumor for which standard therapy does not exist or is no longer effective. Functional and non-functional tumors can be included;

⁃ Phase 1b Optional Dose Expansion RAS-MAPK Pathway Mutation Arm only - Histologically confirmed malignancy with a RAS-MAPK pathway mutation that is metastatic or unresectable and for which standard therapy does not exist or is no longer effective. At least 10 subjects with non-small cell lung cancer (NSCLC) are to be enrolled in this arm.