HR+/HER2- Breast Cancer
Conditions
Keywords
CDK4 inhibitor, CDK4/6 inhibitor
Brief summary
The purpose of this study is to investigate the efficacy and safety of BGB-43395 in combination with letrozole compared with investigator's choice of cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with letrozole in patients with advanced or metastatic hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) who have not received prior systemic treatment for advanced or metastatic disease.
Interventions
DRUGBGB-43395
Administered orally.
DRUGLetrozole
Administered orally.
DRUGAbemaciclib
Administered orally.
DRUGPalbociclib
Administered orally.
DRUGRibociclib
Administered orally.
Sponsors
BeOne Medicines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must be at least 18 years of age or the legal age of consent in the jurisdiction in which the study is taking place at the time of signing the informed consent. * Participants with histologically confirmed locally advanced or metastatic HR+ HER2- breast cancer. * Participants must have a stable Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 1. * Adequate organ function.
Exclusion criteria
* Participants who have received prior systemic treatment in the advanced or metastatic setting. * Participants who have received prior treatment with any selective cyclin-dependent kinase 4 (CDK4) or cyclin-dependent kinase 2 (CDK2) targeting agent, or any other investigational anticancer drug in any disease setting, except for prior investigational or approved SERDs in the adjuvant setting, provided that disease recurrence occurred more than 12 months after the last dose of endocrine-based therapy. * Participants with active leptomeningeal disease or uncontrolled, untreated brain metastasis. Note: Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Determined by Blinded Independent Central Review (BICR) | Up to approximately 4 years | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by BICR per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to approximately 11 years | OS is defined as the time from the date of randomization until the date of death due to any cause. |
| Overall Response Rate (ORR) | Up to approximately 4 years | ORR is defined as the percentage of participants who had a complete response (CR) or partial response (PR), as assessed by BICR per RECIST v1.1. |
| Duration of Response (DOR) | Up to approximately 4 years | DOR is defined as the time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first, as assessed by BICR per RECIST v1.1. |
| PFS Determined by Investigator | Up to approximately 4 years | PFS is defined as the time from first dose until first documentation of progression or death, whichever comes first, as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
| Clinical Benefit Rate (CBR) | Up to approximately 4 years | CBR is defined as the percentage of participants who have a CR, PR, or stable disease maintained for ≥ 24 weeks after randomization (without subsequent anticancer treatment) per RECIST v1.1 . |
| Time to Response (TTR) | Up to approximately 4 years | TTR is defined as the time from treatment initiation to the first response confirmed by BICR per RECIST v1.1. |
| Number of Participants with Adverse Events (AEs) | From first dose of study drug up to 30 days after last dose, up to approximately 11 years | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including laboratory values, vital signs, physical examination findings, and electrocardiogram results. |
| Change from Baseline in European Organisation for Research and Treatment of Cancer (EORTC)-Item Library (IL)454. | Baseline and up to approximately 4 years | The EORTC-IL454 is a questionnaire that asks participants to rate their breast cancer symptoms and the impact of breast cancer on their quality of life (QoL). The EORTC-IL454 is an EORTC Item Library-derived scale set constructed using items from the validated EORTC Quality of Life Questionnaire-Core 30 (QLQ-C30) (a core measure of health-related QoL in cancer patients) and the QLQ-BR23 (its breast cancer-specific module) The EORTC-IL454 contains 26 questions, each answered on a 4-point scale (1 = Not at all; 4 = Very much), and includes 2 functional scales (physical functioning and role functioning), 2 symptom scales (Nausea/Vomiting and Diarrhea), and 1 Global Health Status (GHS)/Quality of Life (QoL) scale, 7 systemic side effects scales, 3 arm symptom scales, and 4 breast-specific symptom scales. The recall period is the past 7 days. Higher scores in GHS and functional scales and lower scores in symptom scales indicate better QoL. |
| Progression-Free Survival 2 (PFS2) | Up to approximately 4 years | PFS2 is defined as the time from randomization until progression on the next line of treatment (ie, first subsequent therapy), as assessed by the investigator, or death due to any cause, whichever occurs first. |
Countries
Australia, Brazil, China, France, Germany, Japan, Malaysia, Poland, Puerto Rico, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed