A Study of HRS2543 in Patients With Advanced Tumors

Study Overview
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Brief Summary
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To assess the safety and tolerability of HRS2543 in patients with advanced tumors and to determine the recommended phase II dose (RP2D) of HRS2543

Official Title
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A Phase I, Multi-Center, Open Label, Dose Escalation/Expansion Study of HRS2543 in Patients With Advanced Tumors

Conditions
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Advanced Tumors

Intervention / Treatment
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* Drug: HRS2543


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-70 years of age, both male and female non standard treatment, invalid the standard treatment or refuse to receive standard treatment in patients with advanced tumors diagnosed by pathology the Eastern Cooperative Oncology Group （ECOG） General status (performance status, PS) of 0-1 the expected lifetime ≥ 3 months Has at least one measurable lesion as defined by RECIST v1.1 Written informed consent is provided by signing the informed consent form Exclusion Criteria: Any previous anti-tumor treatment The toxicity caused by any previous anti-tumor treatment has not recovered to ≤ grade 1 Any other anti-tumor treatment is planned during the study treatment After imaging diagnosis, there were brain tumor lesions According to the judgment of the researcher, there are factors that can not swallow, chronic diarrhea and intestinal obstruction or other factors that can significantly affect the absorption, distribution, metabolism or excretion of drugs Active heart disease was present within 6 months before the first administration of the study Other malignancies occurred within 5 years before the first administration of the study Active HBV or HCV infection The subject had a history of immune deficiency According to the judgment of the researcher, there are concomitant diseases that seriously endanger the safety of the subjects, confuse the analysis of the test results, or affect the subjects to complete the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: HRS2543 monotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRS2543<br> | Drug: HRS2543<br>* Dose-escalation part For the dose-escalation study, five dose cohorts (25 mg , 75 mg , 150 mg , 300 mg , and 450 mg ) of HRS2543 are initially set. Dose-expansion part After the completion of dose-escalation study, the dose-expansion study will be carried out at the recommended dose level by the SMC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-Limiting Toxicity (DLT) | A DLT is considered at AE related to study drug unless there is a clear, well-documented, alternative explanation for the toxicity. Severity of AEs are graded according to the NCI CTCAE 5.0 for the study, the occurrence of the following drug related AEs during the single dose and the first cycle (28 days) will be considered a DLT by the investigator and SMC. | Day 1 to 28 (Cycle 1) | 
| Maximum Tolerated Dose (MTD) | Toxicity will be evaluated according to the NCI CTCAE Version 5.0. | Day 1 to 28 (Cycle 1) | 
| Recommended PhaseII Dose (RP2D) | Toxicity will be evaluated according to the NCI CTCAE Version 5.0. | Day 1 to 28 (Cycle 1) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with changes in laboratory measurements |  | up to 24 months | 
| Number of patients with changes in single and triplicate 12-lead Electrocardiogram (ECG). |  | up to 24 months | 
| Number of patients with changes in ECOG PS score. |  | up to 24 months | 
| Number of patients with changes in Physical Examination. |  | up to 24 months | 
| Number of patients with changes in Vital Signs |  | up to 24 months | 
| Incidence of adverse events (AEs). |  | up to 24 months | 
| Cmax of HRS2543 after single dose of HRS2543 |  | Day 1 of Cycle 1(each cycle 28 days) | 
| Tmax of HRS2543 after single dose of HRS2543 |  | Day 1 of Cycle 1(each cycle 28 days) | 
| AUC0-t of HRS2543 after single dose of HRS2543 |  | Day 1 of Cycle 1(each cycle 28 days) | 
| AUC0-∞ of HRS2543 after single dose of HRS2543 |  | Day 1 of Cycle 1(each cycle 28 days) | 
| t1/2 of HRS2543 after single dose of HRS2543 |  | Day 1 of Cycle 1(each cycle 28 days) | 
| Vz/F of HRS2543 after single dose of HRS2543 |  | Day 1 of Cycle 1(each cycle 28 days) | 
| CL/F of HRS2543 after single dose of HRS2543 |  | Day 1 of Cycle 1(each cycle 28 days) | 
| Cmax,ss of HRS2543 after multiple dose administration of HRS2543 |  | Up to 4 cycles (each cycle 28 days) | 
| Tmax,ss of HRS2543 after multiple dose administration of HRS2543 |  | Up to 4 cycles (each cycle 28 days) | 
| Cmin,ss of HRS2543 after multiple dose administration of HRS2543 |  | Up to 4 cycles (each cycle 28 days) | 
| AUCss of HRS2543 after multiple dose administration of HRS2543 |  | Up to 4 cycles (each cycle 28 days) | 
| Rac of HRS2543 after multiple dose administration of HRS2543 |  | Up to 4 cycles (each cycle 28 days) | 
| ORR: the Objective Response Rate |  | up to 24 months | 
| DoR: the Duration of Response |  | up to 24 months | 
| DCR: the Disease Control Rate |  | up to 24 months | 
| PFS: the Progression Free Survival |  | up to 24 months |