Advanced or Metastatic Solid TumorsPhase 1Luca-1NCT07705334
A Study of SHY-ONC6, a Novel Proteasome Inhibitor, in Adults With Advanced or Metastatic Solid Tumors
A Phase 1 study testing SHY-ONC6 in people with Advanced or Metastatic Solid Tumors and Triple Negative Breast Cancer (TNBC), run by SHY Therapeutics at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumors, Triple Negative Breast Cancer (TNBC), HR+ Breast Cancer
- What is being tested?
- SHY-ONC6
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- 24 Jun 2026to 15 May 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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 .
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- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Clinical Operations contact
United States3 sites, 3 recruiting
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Timothy Yap, MBBS, PhD
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
Ildefonso Rodriguez Rivera, MD
- Recruiting
HonorHealth Research Institute
Scottsdale, Arizona, 85258
Justin Moser, MD
About this study
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
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).
Read the 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).
- Conditions
- Advanced or Metastatic Solid Tumors, Triple Negative Breast Cancer (TNBC), HR+ Breast Cancer, Colon Cancer, Gastric Cancer, Hepatecellular Carcinoma
- Being tested
- SHY-ONC6
- Keywords
- Proteasome Inhibitor, Solid Tumors
- Medical subject headings
- Triple Negative Breast Neoplasms, Colonic Neoplasms, Stomach Neoplasms, Carcinoma, Non-Small-Cell Lung, Mesothelioma, Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SHY-ONC6Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: SHY-ONC6 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 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.
Measured: 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)
Maximum observed plasma concentration of study drug.
Measured: 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)
Area under the plasma concentration-versus-time curve for study drug.
Measured: 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 from dosing to observed maximum plasma concentration of study drug.
Measured: 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)
Terminal elimination half-life of study drug.
Measured: 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)
Plasma concentration of study drug immediately prior to the next dose.
Measured: 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 from first dose until death from any cause.
Measured: 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)
Adverse events and serious adverse events graded per NCI CTCAE v6.0, collected during Phase 1b.
Measured: From first dose through end of treatment plus a 30-day safety follow-up period.
Anti-Tumor Activity - Objective Response Rate
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).
Measured: Baseline through study completion, an average of 18 months.
Anti-Tumor Activity - Best Overall Response (BOR)
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).
Measured: Baseline through study completion, an average of 18 months.
Anti-Tumor Activity - Time to Response (TTR)
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).
Measured: From baseline until first documented response, assessed up to an estimated 18 months.
Anti-Tumor Activity - Duration of Response (DOR)
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).
Measured: Baseline through study completion, an average of 18 months.
Anti-Tumor Activity - Progression-Free Survival
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.
Measured: Baseline through study completion, an average of 18 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2026
- Study start24 Jun 2026
- Primary completion15 May 2027 (estimated)
- Study completion15 May 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- SHY Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07705334
- Sponsor's protocol ID
- SHY-ONC6-101
- Acronym
- Luca-1
- Status last verified
- Oct 2026
- First submitted
- 1 Jul 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No