Advanced Breast Cancer, Advanced Solid Tumor, HER2-negative Breast Cancer, Hormone-receptor-positive Breast Cancer, Hormone Receptor Positive Breast Carcinoma, Hormone Receptor Positive HER-2 Negative Breast Cancer, Hormone Receptor Positive Malignant Neoplasm of Breast, Metastatic Breast Cancer
Conditions
Keywords
breast cancer, advanced solid tumor, advanced breast cancer, hormone receptor positive breast cancer, HER2-negative breast cancer, Hormone Receptor Positive HER-2 Negative Breast Cancer, BGB-43395
Brief summary
This is a dose escalation and dose expansion study to compare how well BGB-43395, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, works as monotherapy or in combination with fulvestrant, letrozole, or elacestrant in participants with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer (BC) and other advanced solid tumors. The main purpose of this study is to explore the recommended dosing for BGB-43395.
Detailed description
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
Interventions
DRUGBGB-43395
Planned doses administered orally.
DRUGFulvestrant
Standard dose administered via intramuscular injection.
DRUGLetrozole
Standard dose administered orally as a tablet.
DRUGElacestrant
Standard dose administered orally as a tablet.
DRUGAnti-Diarrheal Agent
Administered orally as a tablet.
Sponsors
BeOne Medicines
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Phase 1a (Dose Escalation): Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors associated with dependency on CDK4, including HR+ breast cancer, ovarian cancer, endometrial cancer, non-small cell lung cancer, and others. For combination with elacestrant, participants must have received at least 1 prior line of treatment for advanced/metastatic disease including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting. * Phase 1a Safety Expansion: For combination with fulvestrant in regions where approved and available, participants with HR+ breast cancer must have received at least 1 prior line of treatment including endocrine therapy and a CDK4/6 inhibitor. For combination with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease. * Phase 1b: Participants with HR+/HER2- breast cancer. * Phase 1b: For combination with fulvestrant, participants with HR+/HER2- breast cancer enrolled in regions where CDK4/6 inhibitors are approved and available must have received 1-2 lines of therapy for advanced/metastatic disease including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy for advanced disease. For combination cohorts with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease. * Stable Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1. * Female participants with metastatic HR+/HER2- breast cancer must be postmenopausal or receiving ovarian function suppression treatment. * Adequate organ function without symptomatic visceral disease.
Exclusion criteria
* Known leptomeningeal disease or uncontrolled, untreated brain metastases. * Any malignancy ≤ 3 years before the first dose of study treatment(s) except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated with curative intent (eg, resected basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast). * Uncontrolled diabetes. * Infection requiring systemic antibacterial, antifungal, or antiviral therapy ≤ 28 days before the first dose of study drug(s), or symptomatic COVID-19 infection. * Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) at screening. * Participants with active hepatitis C infection. * Prior allogeneic stem cell transplantation, or organ transplantation. Note: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to approximately 60 months | Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria. |
| Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395 | Up to approximately 60 months | MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate of 28%. MAD is defined as the highest dose administered if MTD is not reached. |
| Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395 | Up to approximately 60 months | RDFE of BGB-43395 alone or in combination with fulvestrant, letrozole, or elacestrant will be determined based upon the MTD or MAD. |
| Phase 1b: Objective Response Rate (ORR) | Up to approximately 60 months | ORR is defined as the percentage of participants who have confirmed complete response (CR) or partial response (PR) assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: ORR | Up to approximately 60 months | ORR is defined as the percentage of participants who have confirmed CR or PR assessed by the investigator using RECIST v1.1. |
| Phase 1a and 1b: Duration of Response (DOR) | Up to approximately 60 months | DOR is defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator. |
| Phase 1a and 1b: Time to Response (TTR) | Up to approximately 60 months | TTR is defined as the time from the date of the first dose of study drugs to the date of the first determination of objective response by the investigator using RECIST v1.1. |
| Phase 1b: Disease Control Rate (DCR) | Up to approximately 60 months | DCR is defined as the percentage of participants with best overall response of CR, PR, or stable disease assessed by the investigator using RECIST v1.1. |
| Phase 1b: Clinical Benefit Rate (CBR) | Up to approximately 60 months | CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks. |
| Phase 1b: Progression-Free Survival (PFS) | Up to approximately 60 months | PFS is defined as the time from the date of the first dose of study drug(s) to the date of the first documentation of progressive disease assessed by the investigator using RECIST v1.1 or death, whichever occurs first. |
| Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to approximately 60 months | Number of participants with AEs and SAEs, including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments. |
| Phase 1a: Observed Plasma Maximum Concentration (Cmax) of BGB-43395 and its metabolite | From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days) | — |
| Phase 1a: Observed Plasma Trough Concentration (Ctrough) of BGB-43395 and its metabolite | From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days) | — |
| Phase 1a: Area under the concentration-time curve (AUC) of BGB-43395 and its metabolite | From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days) | — |
| Phase 1a: Half-life (t1/2) of BGB-43395 and its metabolite | From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days) | — |
| Phase 1b: Plasma concentrations of BGB-43395 and its metabolite | From Cycle 1 Day 1 up to Cycle 5 Day 1 (each cycle is 28 days) | — |
Countries
Australia, Brazil, China, France, Japan, Malaysia, Moldova, New Zealand, South Korea, Thailand, United States
Contacts
CONTACTStudy Director
STUDY_DIRECTORStudy Director
BeOne Medicines
Outcome results
None listed