BGB-43395 Alone or as Part of Combination Therapies in Chinese Participants With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

A Phase 1a/1b Study Investigating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of the CDK4 Inhibitor BGB-43395, Alone or as Part of Combination Therapies in Chinese Patients With Advanced or Metastatic HR+/HER2- Breast Cancer and Other Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06253195
• Other study ID #: BGB-43395-102
• Secondary ID: CTR20240674
• Status: Recruiting
• Phase: Phase 1
• Start date: April 1, 2024
• Est. completion date: October 26, 2026

Study information

• Verified date: May 2024
• Source: BeiGene
• Contact: Study Director
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 78
• Est. completion date: October 26, 2026
• Est. primary completion date: February 28, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Breast Cancer
• Breast Neoplasms
• HER2-negative Breast Cancer
• Hormone Receptor Positive Malignant Neoplasm of Breast
• Metastatic Breast Cancer
• Metastatic Solid Tumor
• Neoplasms

Intervention

Drug:
• BGB-43395
Administered orally.
• Fulvestrant
Administered via intramuscular injection.
• Letrozole
Administered orally.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing	Beijing
China	Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)	Guangzhou	Guangdong
China	Shandong Cancer Hospital	Jinan	Shandong
China	The First Affiliated Hospital of Nanchang University Branch Donghu	Nanchang	Jiangxi
China	Guangxi Medical University Cancer Hospital	Nanning	Guangxi
China	Fudan University Shanghai Cancer Center	Shanghai	Shanghai
China	The First Hospital of China Medical University	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Up to approximately 30 months
Primary	Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395	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.	Up to approximately 30 months
Primary	Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395	RDFE of BGB-43395 alone or as part of combination therapies will be determined based upon the MTD or MAD.	Up to approximately 30 months
Primary	Phase 1b: Objective Response Rate (ORR)	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.	Up to approximately 30 months
Secondary	Phase 1a: ORR	ORR is defined as the percentage of participants who have confirmed CR or PR assessed by the investigator using RECIST v1.1.	Up to approximately 30 months
Secondary	Phase 1b: Progression-Free Survival (PFS)	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.	Up to approximately 30 months
Secondary	Phase 1b: Number of Participants with AEs and SAEs	Number of participants with AEs and SAEs including findings from physical examinations, ECGs, and laboratory assessments as needed.	Up to approximately 30 months
Secondary	Phase 1a and 1b: Duration of Response (DOR)	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.	Up to approximately 30 months
Secondary	Phase 1a and 1b: Time to Response (TTR)	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.	Up to approximately 30 months
Secondary	Phase 1b: Disease Control Rate (DCR)	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.	Up to approximately 30 months
Secondary	Phase 1b: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting = 24 weeks.	Up to approximately 30 months
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)