A Study of GB491 in Combination With Letrozole in Patients With HR Positive and HER2 Negative Advanced Breast Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the efficacy and safety of GB491 combined with Letrozole versus placebo combined with Letrozole in the treatment of HR+/HER2- locally advanced or metastatic breast cancer without prior systemic antitumor therapy

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase III Trial of GB491 in Combination With Letrozole in Subjects With HR Positive and HER2 Negative Locally Advanced or Metastatic Breast Cancer Who Have Not Previously Received Systemic Therapy in This Disease Setting

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: GB491 combined with Letrozole
* Drug: Placebo combined with Letrozole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age: 18-75 years old; Have a pathologically-confirmed diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer; No previous systematic antitumor therapy for locally advanced or metastatic breast cancer; Eastern Cooperative Oncology Group [ECOG] 0-1; Have adequate organ and marrow function; Agree to sign the informed consent; Exclusion Criteria: Systematic treatment with any other CDK4/6 inhibitor； Subjects with known allergy to GB491 or any component of Letrozole； Confirmed diagnosis of HER2 positive disease; Known uncontrolled, or symptomatic central nervous system metastases; Had major surgery (or is expected to require major surgery during the study period), chemotherapy, radiation, any investigational drug, or other antitumor therapy within 4 weeks prior to randomization; Have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer; Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure, or ventricular arrhythmia which need medical intervention； Known history of HIV infection or HIV seropositivity (including HIV antibody positive at the time of screening)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GB491 combined with Letrozole<br> | Drug: GB491 combined with Letrozole<br>* Patients were randomized to receive GB491 150 mg orally twice daily, depending on their assignment. Letrozole 2.5 mg orally once a day from the first day of cycle 1 (one cycle every 28 days)<br>|
| Placebo Comparator: Placebo combined with Letrozole<br> | Drug: Placebo combined with Letrozole<br>* Patients were randomized to receive placebo orally twice daily, depending on their assignment. Letrozole 2.5 mg orally once a day from the first day of cycle 1 (one cycle every 28 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-assessed PFS based on RECIST v1.1 | To evaluate progression-free survival (PFS) of GB491 plus Letrozole versus placebo plus Letrozole in HR+/HER2- locally advanced or metastatic breast cancer without prior systemic antitumor therapy (as assessed by the investigator). | Approximately 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BICR-assessed PFS based on RECIST v1.1. |  | Approximately 60 months | 
| OS |  | Approximately 60 months | 
| ORR |  | Approximately 60 months | 
| DOR |  | Approximately 60 months | 
| DCR |  | Approximately 60 months | 
| CBR |  | Approximately 60 months | 
| Number of Participants With adverse events (AEs) and serious adverse events (SAEs) Incidence, nature, and severity of adverse events graded according to the NCI CTCAE v5.0 |  | Approximately 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HR+/HER2-, locally advanced or metastatic breast cancer, GB491