A Single Arm, Open, Multicenter Phase I Clinical Study on the Safety, Tolerance, and Pharmacokinetics of HRS-2189 Single Drug in Patients With Advanced Malignant Solid Tumors

Shandong Suncadia Medicine Co., Ltd.1 site in 1 country60 target enrollmentMay 26, 2023

ConditionsAdvanced Malignant Tumor

InterventionsHRS-2189 Tablets

DrugsHRS-2189 Tablets

Overview

Phase: Phase 1
Intervention: HRS-2189 Tablets
Conditions: Advanced Malignant Tumor
Sponsor: Shandong Suncadia Medicine Co., Ltd.
Enrollment: 60
Locations: 1
Primary Endpoint: Recommended Phase II Dose (RP2D) of HRS-2189
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is a multi center, open label, dose increasing/dose expanding/efficacy expanding phase I clinical trial aimed at evaluating the safety, tolerance, PK characteristics, and anti-tumor efficacy characteristics of HRS-2189 single drug in patients with advanced malignant solid tumors. This study was divided into three stages: dose escalation, dose expansion, and efficacy expansion.

Registry

clinicaltrials.gov

Start Date

May 26, 2023

End Date

December 31, 2025

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Shandong Suncadia Medicine Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Volunteer to participate in this study, sign an informed consent form, have good compliance, and can cooperate with follow-up
•Age ≥ 18 years old (including boundary value, calculated based on the date of signing informed consent), Male or female
•ECOG score: 0-1
•Expected survival ≥ 12 weeks
•Local recurrent or metastatic advanced malignant solid tumor confirmed by histopathology or cytopathology and not resectable, and currently fails to undergo standard treatment or has no standard treatment plan
•If enrolled in ER positive and HER2 negative female breast cancer subjects, they need to meet the criteria defined in the guidelines of the American Association of Clinical Oncology/American College of Pathologists
•Baseline presence of at least one extracranial measurable lesion that meets the RECIST v1.1 standard
•The functional level of important organs is basically normal, meeting the requirements of the scheme
•Previous treatment: Before the first medication in this study, the interval between receiving nitrosourea or mitomycin C ≥ 6 weeks; Receiving cytotoxic drugs, endocrine therapy, immunotherapy, targeted therapy, surgical interval (except puncture biopsy or PICC catheterization or PORT infusion port catheterization) or other clinical studies with the last medication ≥ 4 weeks; Interval from the end of radiotherapy ≥ 2 weeks
•Adverse events caused by other treatments for the subject returned to a severity level of NCI-CTCAE V5.0 ≤ 1 (excluding hair loss and other adverse events judged tolerable by the investigator)

Exclusion Criteria

•Subjects with cancerous meningitis or untreated central nervous system metastasis
•Uncontrolled pleural, abdominal, and pericardial effusion
•Clinical symptoms or diseases of the heart that are not well controlled
•Arterial/venous thrombotic events occurred within 6 months before the first medication administration
•Active infection or unexplained fever\>38.5 ° C occurred within 4 weeks before or on the day of the first medication (subjects with tumor fever are judged by the investigator to be included in the study)
•Subjects with congenital or acquired immune dysfunction (such as HIV infected persons); Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
•Subject has active hepatitis
•Subjects had other malignant tumors within the past 3 years, except for fully treated basal or squamous cell skin cancer or cervical carcinoma in situ
•Those who are unable to swallow tablets normally or have gastrointestinal dysfunction that may affect drug absorption according to the judgment of the researcher
•Patients participating in the QT/QTc study have used any medication that has the risk of prolonging the QT/QTc interval or causing torsade de pointe (TdP) within 4 weeks before the first medication, have a previous history of congenital QT interval prolongation syndrome or a family history of QT interval prolongation, have an implanted pacemaker or automatic implantable cardioverter defibrillator, and cannot correct electrolyte disturbances that affect the QT/QTc study

Arms & Interventions

HRS-2189 Tablets

Intervention: HRS-2189 Tablets

Outcomes

Primary Outcomes

Recommended Phase II Dose (RP2D) of HRS-2189

Time Frame: up to 35 days

AEs+SAEs

Time Frame: from the first drug administration to within 30 days for the last treatment dose

Dose limited toxicity (DLT) of HRS-2189

Time Frame: up to 35 days

Maximum tolerated dose（MTD）of HRS-2189

Time Frame: up to 35 days

Secondary Outcomes

Progression free survival（PFS）(every 8 weeks since Day 8 administration,an average of 1 year)
Evaluation of pharmacokinetic parameter of HRS-2189: Tmax(2 months)
Evaluation of pharmacokinetic parameter of HRS-2189: AUC0-t(2 months)
Evaluation of pharmacokinetic parameter of HRS-2189: Cmax(2 months)
Evaluation of pharmacokinetic parameter of HRS-2189: Tmax,ss(2 months)
Evaluation of pharmacokinetic parameter of HRS-2189: Cmin,ss(2 months)
Disease control rate (DCR)(every 8 weeks since Day 8 administration,an average of 1 year)
Evaluation of pharmacokinetic parameter of HRS-2189: Cmax,ss(2 months)
Evaluation of pharmacokinetic parameter of HRS-2189: AUCss(2 months)
Objective Response Rate (ORR)(every 8 weeks since Day 8 administration,an average of 1 year)
Evaluation of pharmacokinetic parameter of HRS-2189: AUC0-inf(2 months)
Evaluation of pharmacokinetic parameter of HRS-2189: Rac(2 months)
Bioavailability of HRS-2189 on an empty stomach and after meals(up to 9 days)
Duration of response (DoR)(every 8 weeks since Day 8 administration,an average of 1 year)