SHR9549 in ER Positive HER2 Negative Advanced Breast Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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

Official Title
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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

Conditions
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ER+ HER2- Advanced Breast Cancer

Intervention / Treatment
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* Drug: SHR9549


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |