A Study of SHY-ONC6, a Novel Proteasome Inhibitor, in Adults With Advanced or Metastatic Solid Tumors

Inclusion Criteria: * Male or female ≥18 years of age. * Life expectancy \>3 months. * ECOG performance status 0-1. * Histologically/cytologically confirmed advanced or metastatic solid tumors that have progressed on or are intolerant/unsuitable for standard therapies. Eligible tumor types: TNBC, HR+ breast cancer, colon cancer, gastric cancer, HCC, NSCLC (adeno and squamous), mesothelioma, pancreatic cancer, HRPC, soft tissue sarcoma; other tumor types after Medical Monitor discussion. Stable CNS metastases ≥4 weeks post-radiotherapy and off steroids ≥14 days are permitted. * ≥1 measurable lesion per RECIST v1.1 (prostate cancer with bone-only disease and elevated PSA assessed by PCWG3). * Accessible tumor for biopsy * Adequate organ/bone marrow function. * Willingness and ability to provide informed consent. * Negative serum pregnancy test and use of effective contraception through 90 days after last dose for women of childbearing potential. * Male participants must use barrier contraception or abstinence and not donate sperm through 90 days after last dose. Exclusion Criteria: * High-risk cardiovascular disease. * Concurrent anti-cancer treatment. * Active infection requiring systemic treatment within 2 weeks pre-dose. * History of another malignancy (with standard exceptions for in situ disease, non-melanoma skin cancers, and remission ≥2 years). * Active HBV (HBV-DNA \>ULN), HCV (HCV-RNA \>ULN), or HIV (well-controlled HIV with CD4 ≥350 cells/µL and undetectable viral load permitted); AIDS-defining opportunistic infection within 12 months. * Compromised pulmonary function within 6 months pre-dose . * Pregnancy or breastfeeding. * Recent radiotherapy, systemic anti-tumor therapy, other investigational therapy without appropriate washout. * Major surgery ≤4 weeks pre-dose. * Unable to swallow tablets or conditions affecting GI absorption. * Any medical or psychiatric disorders affecting compliance and/or interpretation of study results. * Persistent toxicities from prior anti-cancer therapy (exceptions apply) * Clinically significant corneal disease. * Unable to comply with prohibited concomitant medication restrictions.