A Trial of HRS-1358 Tablets in Metastatic or Local Advanced Breast Cancer

A Single-arm, Open-label, Multi-center Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HRS-1358 Monotherapy or Combination With Dalpiciclib Isethionate Tablets in Patients With Metastatic or Locally Advanced Breast Cancer.

The study is being conducted to evaluate the safety and tolerability of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets in patients 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).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: HRS-1358

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xia Zhang; Phone Number: +0518-81220121; Email: Xia.zhang@hengrui.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Recruiting
      • Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
      • Principal Investigator: Binghe Xu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Histologically diagnosis of local advanced or metastatic breast cancer
2. Women must be postmenopausal, or pre-/peri-menopausal women must be on ovarian suppression
3. At least 1 line of endocrine therapy in the metastatic or advanced setting
4. ECOG performance status score: 0-1;
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. the investigators judged that it was not suitable to endocrine therapy
2. patients with active brain metastasis (without medical control or with clinical symptoms),
3. History of clinically significant cardiovascular or cerebrovascular diseases
4. The subject has one of many factors affecting oral 、absorption, distribution, metabolism and excretion of drugs
5. Active autoimmune diseases, History of immunodeficiency, including positive HIV serum test result and other acquired or congenital immunodeficiency diseases, or history of organ transplantation
6. Have received other similar drugs in the past;
7. Known history of allergy to HRS-1358 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: HRS-1358; Daily oral dosages of HR-1358； Daily oral dosages of HR-1358 and Dalpiciclib Isethionate Tablets	Drug: HRS-1358; HRS-1358 or combination with Dalpiciclib Isethionate Tablets will be administered daily orally in continuous dosing over 28-day cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Dose Limited Toxicities (DLTs)	Number of participants with dose-limiting toxicities (DLTs)	up to 28 days
Maximum tolerated dose	The Maximum tolerated dose of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	up to 28 days
RP2D	select the Recommended Phase 2 Dose (RP2D) of HRS-1358 or combination with Dalpiciclib Isethionate Tablets	Change From Baseline at 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) in participants		Up to approximately 1 year
Clinical benefit rate (CBR) in participants		Up to approximately 1 year
Duration of response (DOR) in participants		Up to approximately 1 year
Progression Free Survival (PFS) observed in participants		Up to approximately 1 year
Cmax	PK parameters of multiple doses of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period
Tmax	PK parameters of multiple doses of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period
AUC0-t	PK parameters of multiple doses of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period
Cmax,ss	PK parameters of multiple doses of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period
Tmax,ss	PK parameters of multiple doses of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period
Cmin,ss	PK parameters of multiple doses of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period
AUCss	PK parameters of multiple doses of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period
Rac	PK parameters of multiple doses of HRS-1358 monotherapy or combination with Dalpiciclib Isethionate Tablets	0.5 hour before first dose of first treatment period to the 0.5 hour before first dose of fourth treatment period

Collaborators and Investigators

• Sponsor: Shandong Suncadia Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: November 17, 2022
• First Submitted That Met QC Criteria: November 17, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: HRS-1358-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