A Trial of HRS-8080 Tablets in Metastatic or Local Advanced Breast Cancer of Adults

A Single-arm, Open-label and Multi-center Phase I Study on Safety, Tolerance and Pharmacokinetics of HRS-8080 Tablets Monotherapy and Combined With Other Anti-cancer Therapy in Patients With Metastatic or Local Advanced Breast Cancer

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Metastatic or Local Advanced Breast Cancer of Patients
• Intervention / Treatment: Drug: HRS-8080 tablets、SHR 6390 tablets、Abemaciclib、Everolimus

• Study Type: Interventional
• Enrollment (Anticipated): 156
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • Fifth Medical Center of People's Liberation Army of China General Hospital
  • Jilin
    • Changchun, Jilin, China, 130012
      • Jilin Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Group; Firstly Dose Escalation and Dose Expansion of HRS-8080 monotherapy should be conducted. After RP2D and MTD of the HRS-8080 monotherapy were confirmed, Dose Escalation and Dose Extension of HRS-8080 in combination with other anti-cancer treatment would be completed, including SHR 6390, or Abemaciclib, or Everolimus.	Drug: HRS-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose	The Maximum tolerated dose of HRS-8080 monotherapy or in combination with SHR-6390 / Abemaciclib / Everolimus	up to 28 days
Recommended phase II dose	The Recommended phase II dose of HRS-8080 monotherapy or in combination with SHR-6390 / Abemaciclib / Everolimus	up to 28 days
Incidence and severity of adverse events (AEs)/serious adverse events (SAEs)	Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) graded by Common Terminology Criteria for Adverse Events (CTCAE) v5.0	up to 30 days after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus.	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period
Tmax	PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus. etc.	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period
AUC0-t	PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus.	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period
Cmax,ss	PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus.	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period
Tmax,ss	PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus.	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period
Cmin,ss	PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus.	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period
AUCss	PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus.	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period
Rac	PK parameters of multiple doses of HRS-8080 monotherapy. HRS-8080 in combination therapy, SHR-6390, Abemaciclib and Everolimus.	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fifth treatment period
ORR	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	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
BOR	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	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
DoR	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	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
DCR	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	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
PFS	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	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

Collaborators and Investigators

• Sponsor: Shandong Suncadia Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2022
• Primary Completion (Anticipated): October 31, 2024
• Study Completion (Anticipated): July 31, 2025

Study Registration Dates

• First Submitted: December 16, 2021
• First Submitted That Met QC Criteria: December 30, 2021
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): April 5, 2022
• Last Update Submitted That Met QC Criteria: April 2, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Everolimus
• Other Study ID Numbers: HRS-8080-I-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No