SHR9549 in ER Positive HER2 Negative Advanced Breast Cancer

Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of SHR9549 in Women With ER Positive HER2 Negative Advanced Breast Cancer

This is a phase 1 open label multicentre study of SHR9549 administered orally in patients with advanced estrogen receptor (ER) positive human epidermal receptor 2 (HER2) negative breast cancer. The study design allows an escalation of dose with intensive safety monitoring to ensure the safety of patients. The study will determine the maximum tolerated dose(MTD). In addition, expansion cohort(s) at potential therapeutic dose(s) in patients will be enrolled to further determine the safety, tolerability, pharmacokinetics and biological activity of SHR9549.

Study Overview

• Status: Terminated
• Conditions: ER+ HER2- Advanced Breast Cancer
• Intervention / Treatment: Drug: SHR9549

Detailed Description

A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of SHR9549 in Women with Estrogen Receptor (ER) Positive Human Epidermal Receptor (HER-2) Negative Advanced Breast Cancer

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100071
      • The 307th Hospital of Military Chinese People's Liberation Army

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Aged 18-70 years.
• Confirmation of ER positive; HER2 negative Advanced breast cancer
• Documented disease progression after at least 6 months prior endocrine therapy for ER positive breast cancer.
• Receipt of ≤2 lines of prior chemotherapy for advanced disease.
• Any menopausal status.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 and with minimum life expectancy of 12 weeks.

Exclusion Criteria:

• Any anti-cancer drugs for the treatment of advanced breast cancer within 14 days of the first dose of study treatment.
• Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia.
• Patient who is unsuitable for endocrine therapy alone including presence of life-threatening metastatic visceral disease.
• uncontrolled central nervous system metastatic disease.
• Any evidence of severe or uncontrolled systemic diseases.
• Inadequate bone marrow reserve or organ function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SHR9549 dose escalation and expansion(s); Escalating dose of SHR9549 with intensive safety monitoring to ensure the safety of patients	Drug: SHR9549; If initial dosing of SHR9549 is tolerated then subsequent cohorts will test increasing doses until a maximum tolerated dose(MTD) is defined; Other Names: SHR9549 tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose Limited Toxicity (DLT)	to determine DLT in order to assess the tolerability of SHR9549	baseline through 28 days
Maximum Tolerated Dose (MTD)	to determine MTD in order to assess the tolerability of SHR9549	baseline through 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	Single and multiple dose pharmacokinetic parameters of SHR9549 at pre-defined intervals	baseline through 12 weeks
Area under the plasma concentration versus time curve (AUC)	Single and multiple dose pharmacokinetic parameters of SHR9549 at pre-defined intervals	baseline through 12 weeks
overall response rate (ORR)	Antitumour activity by evaluation of tumour response assessments using Response Evaluation Criteria in Solid Tumours (RECIST 1.1)	every 8 weeks for 24 weeks and then every 12 weeks thereafter through study completion, an average of 6 months
progression free survival (PFS)	Antitumour activity evaluation by following up patients' progression and survival	every 8 weeks for 24 weeks and then every 12 weeks thereafter through study completion, an average of 6 months
Incidence of Treatment-Emergent Adverse Events	to assess the safety of SHR9549	baseline through 30 days after study completion

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 25, 2018
• Primary Completion (ACTUAL): October 14, 2019
• Study Completion (ACTUAL): October 14, 2019

Study Registration Dates

• First Submitted: June 25, 2018
• First Submitted That Met QC Criteria: July 12, 2018
• First Posted (ACTUAL): July 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): September 1, 2022
• Last Update Submitted That Met QC Criteria: August 29, 2022
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: SHR9549-I-101

Drug and device information, study documents

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