A Phase 1 Study Evaluating CB-5083 in Subjects With Advanced Solid Tumors

Inclusion Criteria

• •1. Males and females ≥18 years of age;
• •2. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤1
• •3. Acceptable bone marrow and organ function at screening as described below:
• •1. ANC ≥ 1,500/µL;
• •2. Platelet count ≥ 100,000/µL;
• •3. Total bilirubin ≤ 1.5 × ULN or ≤ 3.0 × ULN for subjects with hereditary benign hyperbilirubinemia;
• •4. AST (SGOT) ≤ 3 × ULN (≤ 5 × ULN if liver metastases are present);
• •5. ALT (SGPT) ≤ 3 × ULN (≤ 5 × ULN if liver metastases are present);
• •6. Serum creatinine ≤ 1.5 mg/dL or a measured creatinine clearance ³ 60 mL/min according to Cockcroft-Gault formula
• •4. Left ventricular ejection fraction informed (LVEF) ≥ 55%;
• •5. Ability to swallow and retain oral medications;
• •6. 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
• •7. Willing and able to provide written informed consent and comply with the requirements of the study;
• •8. Phase 1a Dose Escalation only - Histologically confirmed advanced solid tumor for which standard therapy does not exist or is no longer effective
• •9. Food Effect Stage - willing and able to ingest a standard meal
• •10. 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;
• •11. 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;
• •12. 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;
• •13. 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;
• •14. Phase 1b Optional Dose Expansion Advanced RCC Arm only - Histologically confirmed metastatic renal cell carcinoma;
• •15. 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);
• •16. 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;
• •17. 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.
• •18. Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, may interfere with the informed consent process and/or with compliance with the requirements of the study, or may interfere with the interpretation of the study results and, in the Investigator's opinion, would make the subject inappropriate for entry into this study;
• •19. Use of any investigational agents within 28 days or 5 half-lives (whichever is shorter) prior to Baseline;
• •20. A condition that is expected to require concomitant use of any medication listed as prohibited while on study;
• •21. Pregnant or lactating female;
• •22. Women of childbearing potential, or men who partner with a woman of childbearing potential, unless they agree to use dual barrier contraceptive methods which, in the Investigator's opinion, are effective and adequate for that subject's circumstances while on study drug and for 3 months afterward;
• •23. Grade 3 or 4 eye disorder at study entry, unless stable and longstanding (\>3 months) and unlikely to interfere with protocol-required ophthalmology assessments;
• •24. Phase 1b Optional Dose Expansion pNET Arm only - Poorly differentiated pNET;
• •25. Phase 1b Optional Dose Expansion RAS-MAPK Pathway Mutation Arm only - Subjects with primary pancreatic cancer or primary RAS mutated colorectal cancer.