Metastatic or Local Advanced Breast Cancer of Patients
Conditions
Brief summary
The study is being conducted to evaluate the tolerance, and safety of HRS-8080 tablets monotherapy and combined with other anti-cancer therapy for metastatic or local advanced breast cancer in adults. To explore the reasonable dosage of HRS-8080 tablets for metastatic or local advanced breast cancer.
Interventions
DRUGHRS-8080 tablets、SHR 6390 tablets、Abemaciclib、Everolimus
During HRS-8080 monotherapy period, the dose of HRS-8080 would be increasing. In the combination therapy period, HRS-8080 will be administered at flat dose of RP2D-1 and RP2D.
Sponsors
Shandong Suncadia Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
HRS-8080 tablets monotherapy and combined with other anti-cancer therapy
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. ECOG performance status score: 0-1; 2. Histopathologically documented local advanced or metastatic breast cancer ; 3. Female of not childbearing potential must the related requirement; 4. During or after the last systematic therapy before enrolment, disease progression occurred with clinical or radiographical documentation; 5. Adequate organ functions as defined; 6. Ability to understand and voluntarily agrees to participate by giving written informed consent for the study.
Exclusion criteria
1. For the case of symptomatic visceral metastasis, the investigators judged that it was not suitable to use relevant treatment; 2. patients with active brain metastasis (without medical control or with clinical symptoms), cancerous meningitis, spinal cord compression, or patients with a history of primary tumors of the central nervous system ; 3. History of clinically significant cardiovascular or cerebrovascular diseases; 4. The subject has one of many factors affecting oral drugs; 5. Active infection or fever with unknown cause \> 38.5 °C; 6. Active autoimmune diseases, History of immunodeficiency, including positive HIV serum test result and other acquired or congenital immunodeficiency diseases, or history of organ transplantation; 7. Known history of allergy to study drug ingredients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum tolerated dose | up to 28 days | The Maximum tolerated dose of HRS-8080 monotherapy or in combination with SHR-6390 / Abemaciclib / Everolimus |
| Recommended phase II dose | up to 28 days | The Recommended phase II dose of HRS-8080 monotherapy or in combination with SHR-6390 / Abemaciclib / Everolimus |
| Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) | up to 30 days after the last dose | Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax,ss | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period | PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. |
| Tmax,ss | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period | PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. |
| Cmin,ss | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period | PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. |
| AUCss | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period | PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. |
| Rac | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period | PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. |
| Cmax | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period | PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. |
| BOR | from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months | Best Overall Response, Preliminary Efficacy endpoints of HRS-8080 monotherapy or in combination with SHR-6390, Abemaciclib or Everolimus in treatment of patients with metastatic or local advanced breast cancer |
| DoR | from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months | Duration of response, Preliminary Efficacy endpoints of HRS-8080 monotherapy or in combination with SHR-6390, Abemaciclib or Everolimus in treatment of patients with metastatic or local advanced breast cancer |
| DCR | from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months | Disease control rate, Preliminary Efficacy endpoints of HRS-8080 monotherapy or in combination with SHR-6390, Abemaciclib or Everolimus in treatment of patients with metastatic or local advanced breast cancer |
| PFS | from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months | Progression-free survival, Preliminary Efficacy endpoints of HRS-8080 monotherapy or in combination with SHR-6390, Abemaciclib or Everolimus in treatment of patients with metastatic or local advanced breast cancer |
| ORR | from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 8 months | Objective Response Rate, Preliminary Efficacy endpoints of HRS-8080 monotherapy or in combination with SHR-6390, Abemaciclib or Everolimus in treatment of patients with metastatic or local advanced breast cancer |
| Tmax | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period | PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. etc. |
| AUC0-t | 0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period | PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. |
Countries
China
Outcome results
None listed