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

A Phase 1 Multicenter, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SHY-ONC6 in Participants With Advanced or Metastatic Solid Tumors

This is a Phase 1, first-in-human (FIH), open-label, multicenter study designed to evaluate the safety, tolerability, PK, and preliminary anti-tumor activity of SHY-ONC6 in participants with advanced or metastatic solid tumors who have progressed on or are intolerant to standard therapies. The study will consist of 2 parts: a dose escalation part (Phase 1a) and a dose expansion part (Phase 1b).

This is a Phase 1, first-in-human (FIH), open-label, multicenter study designed to evaluate the safety, tolerability, PK, and preliminary anti-tumor activity of SHY-ONC6 in participants with advanced or metastatic solid tumors who have progressed on or are intolerant to standard therapies. The study will consist of 2 parts: a dose escalation part (Phase 1a) and a dose expansion part (Phase 1b).

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.