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

NCT07705334 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SHY-ONC6-101
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 3

Brief Summary

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).

Conditions

Advanced or Metastatic Solid Tumors; Triple Negative Breast Cancer (TNBC); HR+ Breast Cancer; Colon Cancer; Gastric Cancer; Hepatecellular Carcinoma; NSCLC (Advanced Non-small Cell Lung Cancer); Mesothelioma; Pancreatic Carcinoma Metastatic; Hormone Refractory Prostate Cancer; Soft Tissue Sarcomas

Keywords

Proteasome Inhibitor; Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Incidence of Dose-Limiting Toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs)

  Adverse events and serious adverse events graded per NCI CTCAE v6.0; supported by laboratory tests, vital signs, physical examinations, and triplicate 12-lead ECG. Dose-limiting toxicities assessed during Cycle 1 (Days 1 through 21).

  Dose-limiting toxicities assessed from first dose through Day 21 of Cycle 1 (each cycle is 21 days). Adverse events and serious adverse events collected from first dose through 30 days after last dose.

• Maximum Tolerated Dose (MTD)

  MTD determined using the BOIN (Bayesian Optimal Interval) design, with a target dose-limiting toxicity rate of 0.30, based on dose-limiting toxicity incidence observed during Cycle 1.

  Determined at the end of the Cycle 1 dose-limiting toxicity evaluation period (Cycle 1 is 21 days).

• Recommended Phase 2 Dose (RP2D)

  Phase 1a: RP2D range determined from dose-limiting toxicity, adverse event, and serious adverse event incidence together with the MTD determination. Phase 1b: RP2D defined by integrated safety, efficacy, pharmacodynamic, and pharmacokinetic data.

  Phase 1a: at the end of Cycle 1 (each cycle is 21 days). Phase 1b: through end of treatment plus a 30-day safety follow-up period.

Secondary Outcomes (12)

• Maximum Plasma Concentration (Cmax)

  Cycle 1 Day 1; Day 2 (24 hours post-dose); Day 8; and pre-dose on Day 15. Pre-dose and post-dose on Day 1 of subsequent cycles (each cycle is 21 days).

• Area Under the Plasma Concentration-Time Curve (AUC)

  Cycle 1 Day 1; Day 2 (24 hours post-dose); Day 8; and pre-dose on Day 15. Pre-dose and post-dose on Day 1 of subsequent cycles (each cycle is 21 days).

• Time to Maximum Plasma Concentration (Tmax)

  Cycle 1 Day 1; Day 2 (24 hours post-dose); Day 8; and pre-dose on Day 15. Pre-dose and post-dose on Day 1 of subsequent cycles (each cycle is 21 days).

• Terminal Elimination Half-Life (t1/2)

  Cycle 1 Day 1; Day 2 (24 hours post-dose); Day 8; and pre-dose on Day 15. Pre-dose and post-dose on Day 1 of subsequent cycles (each cycle is 21 days).

• Trough Plasma Concentration (Ctrough)

  Pre-dose on Day 15 of Cycle 1 and pre-dose on Day 1 of subsequent cycles (each cycle is 21 days).

Study Arms (1)

SHY-ONC6

EXPERIMENTAL

Participants receive SHY-ONC6 administered orally once daily. Phase 1a, sequential dose levels are evaluated under accelerated titration and BOIN dose-escalation design. In Phase 1b, participants will be evaluated in disease-specific expansion cohorts and receive SHY-ONC6 at the RP2D range identified in Phase 1a.

Drug: SHY-ONC6

Interventions

SHY-ONC6 DRUG

Participants receive SHY-ONC6 administered orally once daily in 21-day cycles. SHY-ONC6 will be administered until the participant withdraws from study, experiences unacceptable toxicity or other safety event, or their disease progresses.

SHY-ONC6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• SHY Therapeutics: lead

Study Sites (3)

SCRI at HCA HealthONE

Denver, Colorado, 80218, United States

NOT YET RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

NOT YET RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Colonic Neoplasms; Stomach Neoplasms; Carcinoma, Non-Small-Cell Lung; Mesothelioma; Sarcoma

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Stomach Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Mesothelial; Neoplasms, Connective and Soft Tissue

Central Study Contacts

Medical Monitor

CONTACT

619-985-2706; shyonc6@shytherapeutics.com

Clinical Operations

CONTACT

shyonc6@shytherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2026
• First Posted: July 15, 2026
• Study Start: June 29, 2026
• Primary Completion (Estimated): May 15, 2027
• Study Completion (Estimated): May 15, 2028
• Last Updated: July 15, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)