Advanced or Metastatic Solid Tumors, Colon Cancer, Gastric Cancer, Hepatecellular Carcinoma, Hormone Refractory Prostate Cancer, HR+ Breast Cancer, Mesothelioma, NSCLC (Advanced Non-small Cell Lung Cancer), Pancreatic Carcinoma Metastatic, Soft Tissue Sarcomas, Triple Negative Breast Cancer (TNBC)
Conditions
Keywords
Proteasome Inhibitor, Solid Tumors
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).
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
DRUGSHY-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.
Sponsors
SHY Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose-Limiting Toxicities (DLTs), Adverse Events (AEs), and Serious Adverse Events (SAEs) | 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). |
| Maximum Tolerated Dose (MTD) | 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. |
| Recommended Phase 2 Dose (RP2D) | 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
| Measure | Time frame | Description |
|---|---|---|
| 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). | Maximum observed plasma concentration of study drug. |
| 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). | Area under the plasma concentration-versus-time curve for study drug. |
| 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). | Time from dosing to observed maximum plasma concentration of study drug. |
| 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). | Terminal elimination half-life of study drug. |
| 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). | Plasma concentration of study drug immediately prior to the next dose. |
| Overall Survival (OS) | 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. |
| Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) (Phase 1b) | 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. |
| Anti-Tumor Activity - Objective Response Rate | 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). |
| Anti-Tumor Activity - Best Overall Response (BOR) | 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). |
| Anti-Tumor Activity - Time to Response (TTR) | 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). |
| Anti-Tumor Activity - Duration of Response (DOR) | 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). |
| Anti-Tumor Activity - Progression-Free Survival | 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. |
Countries
United States
Contacts
CONTACTMedical Monitor
CONTACTClinical Operations
Outcome results
None listed