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The study is to assess safety and tolerability of HRS8807 monotherapy and in combination with SHR6390 in subjects with metastatic or locally advanced breast cancer in order to estimate the Dose-Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD) and select the Recommended Phase 2 Dose (RP2D).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | HRS8807 monotherapy dose escalation |
|
| Group B | Experimental | HRS8807 monotherapy dose expansion |
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| Group C | Experimental | HRS8807 in combination with SHR6390 dose escalation |
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| Group D | Experimental | HRS8807 in combination with SHR6390 dose expansion |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HRS8807 | Drug | HRS8807 monotherapy |
| |
| HRS8807 |
| Measure | Description | Time Frame |
|---|---|---|
| MTD | Maximum Tolerated Dose (MTD) of HRS8807 monotherapy and in combination with SHR6390 | Change From Baseline at 28 days |
| RP2D | select the Recommended Phase 2 Dose (RP2D) of HRS8807 monotherapy and in combination with SHR6390 | Change From Baseline at 28 days |
| Adverse events (AE) and serious AE (SAE) | AEs and SAEs as characterized by frequency and severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE version 5.0]). | Up to 30 days after end of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Tmax of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) | |
| Cmax of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Shanghai | Shanghai Municipality | 200032 | China |
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HRS8807 monotherapy and in combination with SHR6390
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| Drug |
HRS8807 monotherapy |
|
| HRS8807、SHR6390 | Device | HRS8807 in combination with SHR6390 |
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| HRS8807、SHR6390 | Drug | HRS8807 in combination with SHR6390 |
|
| AUC0-t of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| AUC0-∞ of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| t1/2 of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| Vz/F of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| CL/F of HRS8807 and the major metabolite after single dose of HRS8807 | Day 1, Day 2, Day 3 of single dose (3 days before Cycle1) |
| Tmax,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Cmax,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Cmin,ss of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Rac of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| AUCss of HRS8807 and the major metabolite after multiple dose administration of HRS8807 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Tmax of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390 | Cycle 1 Day 1, Day 2, each cycle is 28 days |
| Cmax of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390 | Cycle 1 Day 1, Day 2, each cycle is 28 days |
| AUC0-t of HRS8807, the major metabolite and SHR6390 after single dose administration of HRS8807 and SHR6390 | Cycle 1 Day 1, Day 2, each cycle is 28 days |
| Tmax,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Cmax,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Cmin,ss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| AUCss of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Rac of HRS8807, the major metabolite and SHR6390 after multiple dose administration of HRS8807 and SHR6390 | Cycle 1 Day 14, Day 15, each cycle is 28 days |
| Objective Response Rate (ORR) | baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant |
| Duration of Response (DoR) | baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant |
| Progression Free Survival (PFS) | baseline to the date of first documentation of progression, assessed approximately up to 6 months after the last entered participant |