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NCT Number: NCT07705334

A Study of SHY-ONC6, a Novel Proteasome Inhibitor, in Adults 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).

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Key information

Conditions

Advanced or Metastatic Solid Tumors Adenoma Breast Diseases Breast Neoplasms Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Colon Cancer Colonic Diseases Colonic Neoplasms Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastric Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms HR+ Breast Cancer Hepatecellular Carcinoma Hormone Refractory Prostate Cancer Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Mesothelioma NSCLC (Advanced Non-small Cell Lung Cancer) Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Connective and Soft Tissue Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Pancreatic Carcinoma Metastatic Respiratory Tract Diseases Respiratory Tract Neoplasms Sarcoma Skin Diseases Skin and Connective Tissue Diseases Soft Tissue Sarcomas Stomach Diseases Stomach Neoplasms Thoracic Neoplasms Triple Negative Breast Cancer (TNBC) Triple Negative Breast Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

SCRI at HCA HealthONE, Denver, Colorado, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

Primary outcomes

  1. 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.

    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).

  2. Maximum Tolerated Dose (MTD)

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

    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.

  3. 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.

    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.

Secondary outcomes

  1. 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).

    Maximum observed plasma concentration of study drug.

  2. 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).

    Area under the plasma concentration-versus-time curve for study drug.

  3. 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).

    Time from dosing to observed maximum plasma concentration of study drug.

  4. 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).

    Terminal elimination half-life of study drug.

  5. 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).

    Plasma concentration of study drug immediately prior to the next dose.

  6. 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.

    Time from first dose until death from any cause.

  7. 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.

    Adverse events and serious adverse events graded per NCI CTCAE v6.0, collected during Phase 1b.

  8. Anti-Tumor Activity - Objective Response Rate

    Time frame: Baseline through study completion, an average of 18 months.

    Objective response rate defined as the proportion of patients with a confirmed best overall response of either complete response or partial response, as determined per investigator assessment by RECIST v1.1 (PCWG3 for prostate cancer with bone disease).

  9. Anti-Tumor Activity - Best Overall Response (BOR)

    Time frame: Baseline through study completion, an average of 18 months.

    Best response recorded from first dose until disease progression (complete response, partial response, stable disease, or progressive disease), per RECIST v1.1 (PCWG3 for prostate cancer with bone disease).

  10. Anti-Tumor Activity - Time to Response (TTR)

    Time frame: From baseline until first documented response, assessed up to an estimated 18 months.

    Time from first dose to first documented complete response (CR) or partial response (PR) per RECIST v1.1 (PCWG3 for prostate cancer with bone disease).

  11. Anti-Tumor Activity - Duration of Response (DOR)

    Time frame: Baseline through study completion, an average of 18 months.

    Time from first documented complete response (CR) or partial response (PR) to disease progression or death from any cause, per RECIST v1.1 (PCWG3 for prostate cancer with bone disease).

  12. Anti-Tumor Activity - Progression-Free Survival

    Time frame: Baseline through study completion, an average of 18 months.

    Time from first dose to first documented disease progression per RECIST v1.1 (PCWG3 for prostate cancer with bone disease) or death from any cause.

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Operations

CONTACT

[email protected]

Medical Monitor

CONTACT

[email protected]

619-985-2706

Sponsors and collaborators

Lead sponsor

SHY Therapeutics

Industry

Registry information

Official study 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

Acronym: Luca-1

Important dates

Study start
2026
Primary completion
2027
Study completion
2028
First posted
Jul 15, 2026
Registry last updated
Jul 15, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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