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

Official title

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

Overview

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).

Detailed description

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).

Interventions

• Drug SHY-ONC6
  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.

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs) [Time frame: 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) [Time frame: Determined at the end of the Cycle 1 dose-limiting toxicity evaluation period (Cycle 1 is 21 days).]
• Recommended Phase 2 Dose (RP2D) [Time frame: 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 outcome measures (12)

• Maximum Plasma Concentration (Cmax) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: 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) [Time frame: Pre-dose on Day 15 of Cycle 1 and pre-dose on Day 1 of subsequent cycles (each cycle is 21 days).]
• Overall Survival (OS) [Time frame: From first dose until death, withdrawal, loss to follow-up, or study termination, assessed up to an estimated 12 months after last dose of study drug.]
• Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1b) [Time frame: From first dose through end of treatment plus a 30-day safety follow-up period.]
• Anti-Tumor Activity - Objective Response Rate [Time frame: Baseline through study completion, an average of 18 months.]
• Anti-Tumor Activity - Best Overall Response (BOR) [Time frame: Baseline through study completion, an average of 18 months.]
• Anti-Tumor Activity - Time to Response (TTR) [Time frame: From baseline until first documented response, assessed up to an estimated 18 months.]
• Anti-Tumor Activity - Duration of Response (DOR) [Time frame: Baseline through study completion, an average of 18 months.]
• Anti-Tumor Activity - Progression-Free Survival [Time frame: Baseline through study completion, an average of 18 months.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• HonorHealth Research Institute — Scottsdale
• SCRI at HCA HealthONE — Denver
• The University of Texas MD Anderson Cancer Center — Houston
• NEXT Oncology — San Antonio

Identifiers

NCT: NCT07705334 · SHY-ONC6-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗