Clinical trial NCT06253195: BGB-43395 Alone or as Part of Combination Therapies in Chinese Participants With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Metastatic Solid Tumor
Hormone-receptor-positive Breast Cancer
Breast Cancer
Metastatic Breast Cancer
Hormone Receptor Positive Malignant Neoplasm of Breast
HER2-negative Breast Cancer
Keywords: advanced solid tumor
metastatic solid tumor
BGB-43395
breast cancer
HR+/HER2- breast cancer
hormone receptor positive breast cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2024-02-12
Enrollment: 33
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 30 months
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395
timeFrame: Up to approximately 30 months
measure: Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395
timeFrame: Up to approximately 30 months
measure: Phase 1b: Objective Response Rate (ORR)
timeFrame: Up to approximately 30 months
Secondary outcomes:
measure: Phase 1a: ORR
timeFrame: Up to approximately 30 months
measure: Phase 1b: Progression-Free Survival (PFS)
timeFrame: Up to approximately 30 months
measure: Phase 1b: Number of Participants with AEs and SAEs
timeFrame: Up to approximately 30 months
measure: Phase 1a and 1b: Duration of Response (DOR)
timeFrame: Up to approximately 30 months
measure: Phase 1a and 1b: Time to Response (TTR)
timeFrame: Up to approximately 30 months
measure: Phase 1b: Disease Control Rate (DCR)
timeFrame: Up to approximately 30 months
measure: Phase 1b: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 30 months
measure: Phase 1a: Observed plasma maximum concentration (Cmax) of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
measure: Phase 1a: Observed plasma trough concentration (Ctrough) of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
measure: Phase 1a: Area under the concentration-time curve (AUC) of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
measure: Phase 1a: Half-life (t1/2) of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
measure: Phase 1b: Plasma concentrations of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 5 Day 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
state: Guangdong
city: Nanning
country: China
facility: Guangxi Medical University Cancer Hospital
state: Guangxi
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: