BGB-43395 Alone or as Part of Combination Therapies in Chinese Participants With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors
- Conditions
- Advanced Solid TumorMetastatic Solid TumorHormone-receptor-positive Breast CancerBreast CancerMetastatic Breast CancerHormone Receptor Positive Malignant Neoplasm of BreastHER2-negative Breast Cancer
- Interventions
- Registration Number
- NCT06253195
- Lead Sponsor
- BeiGene
- Brief Summary
This is an open-label, multicenter, phase 1a/1b clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-43395, a cyclin-dependent kinase 4 (CDK4) inhibitor, as monotherapy or in combination with fulvestrant, letrozole, or other combination partners in Chinese participants with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer (BC) and other advanced or metastatic solid tumors.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 33
- Phase 1a (Dose Escalation): Participants with histologically or cytologically confirmed locally advanced or metastatic solid tumors associated with CDK4 dependency, including HR+/HER2- breast cancer. Participants must have received prior standard-of-care therapies for their disease, unless the therapy is not available or not tolerated, or is determined not appropriate based on the investigator's judgment.
- Phase 1b (Dose Expansion): Participants with selected solid tumors including locally advanced or metastatic HR+/HER2- breast cancer.
- Female participants with metastatic HR+/HER2- breast cancer will be required to have ovarian function suppression using gonadotropin-releasing hormone (GnRH) agonists such as goserelin or be postmenopausal.
- Male participants with HR+/HER2- breast cancer will be required to have gonadal suppression using GnRH agonists when being treated with letrozole or fulvestrant.
- Patients must have ≥1 measurable lesion per RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
- Adequate organ function without symptomatic visceral disease.
- Prior therapy selectively targeting CDK4 (prior CDK4/6 inhibitor therapy is permitted).
- Known leptomeningeal disease or uncontrolled untreated brain metastasis.
- Any malignancy ≤ 3 years before the first dose of study drug(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. Patients receiving prophylactic antibiotics (eg, for prevention of urinary tract infection, chronic obstructive pulmonary disease, or for dental extraction) are eligible. Patients who have recovered from symptomatic COVID-19 infection can be rescreened for this study.
- Untreated chronic hepatitis B or active hepatitis C infection.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1a: Dose Escalation BGB-43395 Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole. Phase 1a: Dose Escalation Fulvestrant Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole. Phase 1a: Dose Escalation Letrozole Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole. Phase 1b: Dose Expansion BGB-43395 The recommended dose for expansion (RDFE) for BGB-43395 in combination with fulvestrant from Phase 1a will be evaluated in HR+ breast cancer and selected tumor cohorts. Phase 1b: Dose Expansion Fulvestrant The recommended dose for expansion (RDFE) for BGB-43395 in combination with fulvestrant from Phase 1a will be evaluated in HR+ breast cancer and selected tumor cohorts.
- Primary Outcome Measures
Name Time Method Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) Up to approximately 30 months Number of participants with AEs and SAEs including findings from physical examinations, electrocardiograms (ECGs), and laboratory assessments as needed, 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 30 months MTD is defined as the highest dose evaluated for which estimated toxicity rate is the closest to the target toxicity rate. 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 30 months RDFE of BGB-43395 alone or as part of combination therapies will be determined based upon the MTD or MAD.
Phase 1b: Objective Response Rate (ORR) Up to approximately 30 months ORR is defined as the percentage of participants who have confirmed complete response (CR) or partial response (PR) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- Secondary Outcome Measures
Name Time Method Phase 1a: ORR Up to approximately 30 months ORR is defined as the percentage of participants who have confirmed CR or PR assessed by the investigator using RECIST v1.1.
Phase 1b: Progression-Free Survival (PFS) Up to approximately 30 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 AEs and SAEs Up to approximately 30 months Number of participants with AEs and SAEs including findings from physical examinations, ECGs, and laboratory assessments as needed.
Phase 1a and 1b: Duration of Response (DOR) Up to approximately 30 months DOR is defined as the time from the first determination of an objective response by the investigator using RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first.
Phase 1a and 1b: Time to Response (TTR) Up to approximately 30 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 that is confirmed by a subsequent response as assessed by the investigator using RECIST v1.1.
Phase 1b: Disease Control Rate (DCR) Up to approximately 30 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 30 months CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks.
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)
Trial Locations
- Locations (7)
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Guangxi Medical University Cancer Hospital
🇨🇳Nanning, Guangxi, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Fudan University Shanghai Cancer Center
🇨🇳Shanghai, Shanghai, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
🇨🇳Guangzhou, Guangdong, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China