Clinical trial NCT05851092: Phase I Clinical Study of HRS-2189 in the Treatment of Patients With Advanced Malignant Tumors
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Malignant Tumor
Lead sponsor: Shandong Suncadia Medicine Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-05-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Volunteer to participate in this study, sign an informed consent form, have good compliance, and can cooperate with follow-up
2. Age ≥ 18 years old (including boundary value, calculated based on the date of signing informed consent), Male or female
3. ECOG score: 0-1
4. Expected survival ≥ 12 weeks
5. 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
6. 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
7. Baseline presence of at least one extracranial measurable lesion that meets the RECIST v1.1 standard
8. The functional level of important organs is basically normal, meeting the requirements of the scheme
9. 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
10. 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)
11. Female subjects with fertility must agree to use highly effective contraception during the study treatment period and within 7 months after the last medication; Male subjects must agree to use highly effective contraception during the study treatment period and 4 months after the last medication; Female subjects with fertility must have a negative serum HCG test within 7 days before the first medication in the study, and must be in non lactation. If the serum HCG is weakly positive, it is necessary for the researcher to evaluate and judge it as a non pregnant state, and urine HCG should be tested before medication, with a negative result
12. Volunteer to participate in this clinical trial, willing and able to follow the procedures related to clinical visits and research, understand the research procedures, and have signed informed consent

Exclusion Criteria:

1. Subjects with cancerous meningitis or untreated central nervous system metastasis
2. Uncontrolled pleural, abdominal, and pericardial effusion
3. Clinical symptoms or diseases of the heart that are not well controlled
4. Arterial/venous thrombotic events occurred within 6 months before the first medication administration
5. 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)
6. Subjects with congenital or acquired immune dysfunction (such as HIV infected persons); Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation
7. Subject has active hepatitis
8. 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
9. Those who are unable to swallow tablets normally or have gastrointestinal dysfunction that may affect drug absorption according to the judgment of the researcher
10. 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
11. Pregnant and lactating women, or planning to become pregnant during the study period
12. According to the judgment of the researcher, the subject has other factors that may lead to the forced termination of this study

Primary outcomes:
measure: AEs+SAEs
timeFrame: from the first drug administration to within 30 days for the last treatment dose
measure: Dose limited toxicity (DLT) of HRS-2189
timeFrame: up to 35 days
measure: Maximum tolerated dose（MTD）of HRS-2189
timeFrame: up to 35 days
measure: Recommended Phase II Dose (RP2D) of HRS-2189
timeFrame: up to 35 days
Secondary outcomes:
measure: Evaluation of pharmacokinetic parameter of HRS-2189: Cmax
timeFrame: 2 months
measure: Evaluation of pharmacokinetic parameter of HRS-2189: Tmax
timeFrame: 2 months
measure: Evaluation of pharmacokinetic parameter of HRS-2189: AUC0-t
timeFrame: 2 months
measure: Evaluation of pharmacokinetic parameter of HRS-2189: AUC0-inf
timeFrame: 2 months
measure: Evaluation of pharmacokinetic parameter of HRS-2189: Cmax,ss
timeFrame: 2 months
measure: Evaluation of pharmacokinetic parameter of HRS-2189: Tmax,ss
timeFrame: 2 months
measure: Evaluation of pharmacokinetic parameter of HRS-2189: Cmin,ss
timeFrame: 2 months
measure: Evaluation of pharmacokinetic parameter of HRS-2189: AUCss
timeFrame: 2 months
measure: Evaluation of pharmacokinetic parameter of HRS-2189: Rac
timeFrame: 2 months
measure: Bioavailability of HRS-2189 on an empty stomach and after meals
timeFrame: up to 9 days
measure: Objective Response Rate (ORR)
timeFrame: every 8 weeks since Day 8 administration,an average of 1 year
measure: Duration of response (DoR)
timeFrame: every 8 weeks since Day 8 administration,an average of 1 year
measure: Disease control rate (DCR)
timeFrame: every 8 weeks since Day 8 administration,an average of 1 year
measure: Progression free survival（PFS）
timeFrame: every 8 weeks since Day 8 administration,an average of 1 year
Other outcomes:
Locations:
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
Study officials:
References: