Advanced Tumors
Conditions
Brief summary
To assess the safety and tolerability of HRS2543 in patients with advanced tumors and to determine the recommended phase II dose (RP2D) of HRS2543
Interventions
DRUGHRS2543
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.
Sponsors
Shanghai Hengrui Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
HRS2543 monotherapy
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. 18-70 years of age, both male and female 2. non standard treatment, invalid the standard treatment or refuse to receive standard treatment in patients with advanced tumors diagnosed by pathology 3. the Eastern Cooperative Oncology Group （ECOG） General status (performance status, PS) of 0-1 4. the expected lifetime ≥ 3 months 5. Has at least one measurable lesion as defined by RECIST v1.1 6. Written informed consent is provided by signing the informed consent form
Exclusion criteria
1. Any previous anti-tumor treatment 2. The toxicity caused by any previous anti-tumor treatment has not recovered to ≤ grade 1 3. Any other anti-tumor treatment is planned during the study treatment 4. After imaging diagnosis, there were brain tumor lesions 5. 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 6. Active heart disease was present within 6 months before the first administration of the study 7. Other malignancies occurred within 5 years before the first administration of the study 8. Active HBV or HCV infection 9. The subject had a history of immune deficiency 10. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended PhaseII Dose (RP2D) | Day 1 to 28 (Cycle 1) | Toxicity will be evaluated according to the NCI CTCAE Version 5.0. |
| Dose-Limiting Toxicity (DLT) | Day 1 to 28 (Cycle 1) | 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. |
| Maximum Tolerated Dose (MTD) | Day 1 to 28 (Cycle 1) | Toxicity will be evaluated according to the NCI CTCAE Version 5.0. |
Secondary
| Measure | Time frame |
|---|---|
| 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) |
| Number of patients with changes in laboratory measurements | up to 24 months |
| 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 |
| CL/F of HRS2543 after single dose of HRS2543 | Day 1 of Cycle 1(each cycle 28 days) |
| 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 |
Countries
China
Outcome results
None listed