Investigational Drug
BGB-43395
TrialFetch AI Analysis
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Overview
BGB-43395 is an investigational, orally administered, selective cyclin-dependent kinase 4 (CDK4) inhibitor being developed by BeOne Medicines, formerly BeiGene. It is being studied alone and with endocrine therapies for HR-positive/HER2-negative breast cancer and other CDK4-dependent solid tumors. The principal first-in-human study is an ongoing phase 1a/1b trial (NCT06120283). (cancer.gov)
Mechanism of action
BGB-43395 inhibits cyclin D–CDK4 activity, reducing phosphorylation of retinoblastoma protein and thereby blocking G1-to-S cell-cycle progression. It was designed to spare CDK6, potentially permitting sustained CDK4 inhibition with less hematologic toxicity than dual CDK4/6 inhibition. Preclinical studies demonstrated inhibition of RB1 phosphorylation, cell proliferation and xenograft growth, including enhanced activity when combined with fulvestrant. These findings have not yet been confirmed in randomized clinical trials. (cancer.gov)
Efficacy
Preliminary phase 1 results are available for BGB-43395 plus letrozole as first-line treatment in 58 CDK4/6 inhibitor–naive patients with advanced HR-positive/HER2-negative breast cancer. In the initial analysis, investigator-assessed objective response rates were 58%, 68% and 40% at 240, 400 and 600 mg twice daily, respectively; disease-control rates were 95%, 100% and 95%. Median progression-free survival had not been reached after 6.8 months’ median follow-up. Responses in that analysis were not necessarily confirmed. (ascopubs.org)
An updated April 30, 2026 analysis reported confirmed objective response rates of 68.4% at 240 mg and 63.2% at 400 mg, although each cohort contained only 19 patients and follow-up remained limited. No randomized efficacy comparison has been reported. (beonemedaffairs.com)
Safety
In the initial 58-patient analysis, treatment-emergent adverse events occurred in 98% of patients. Grade 3 or higher events occurred in 32%, 37% and 65% at 240, 400 and 600 mg, respectively. The most frequent events were diarrhea, nausea and vomiting; grade 3 diarrhea increased with dose—5%, 11% and 30%, respectively. Neutropenia was generally uncommon and low grade, although grade 3 neutropenia occurred in 10% at 600 mg. Adverse events led to dose modification in 53%, treatment discontinuation in 3%, and no deaths. (beonemedinfo.com)
Further reading
- ASCO 2026 phase 1 clinical abstract
- ASCO 2026 updated clinical poster
- Preclinical characterization in Clinical Cancer Research
- NCT06120283 trial record
Last updated: Sep 2026
Active trials using BGB-43395
Found 4 active trials using this drug:
TrialFetch AI summary: Adults with locally advanced or metastatic HR-positive, HER2-negative breast cancer who have not received systemic therapy for advanced disease are randomized to letrozole plus BGB-43395, a selective CDK4 inhibitor, or letrozole plus investigator’s choice of abemaciclib, palbociclib, or ribociclib.
ClinicalTrials.gov ID: NCT07492641
TrialFetch AI summary: Adults with HR-positive/HER2-negative metastatic breast cancer after at least two prior lines of therapy, including endocrine therapy and a CDK4/6 inhibitor, receive oral BGB-21447, a BCL2 inhibitor, plus fulvestrant, with or without BGB-43395, a selective CDK4 inhibitor. The study evaluates safety, dosing, and preliminary antitumor activity.
ClinicalTrials.gov ID: NCT06756932
TrialFetch AI summary: Adults with previously treated advanced solid tumors may receive the oral selective CDK2 inhibitor BG-68501 alone; expansion cohorts focus on HR-positive/HER2-negative breast cancer and platinum-resistant or -refractory serous ovarian, fallopian tube, or primary peritoneal cancer. Breast cancer cohorts also evaluate BG-68501 with fulvestrant, with or without the investigational selective CDK4 inhibitor BGB-43395.
ClinicalTrials.gov ID: NCT06257264
TrialFetch AI summary: Adults with advanced or metastatic CDK4-dependent solid tumors, including HR-positive/HER2-negative breast cancer, receive the investigational oral selective CDK4 inhibitor BGB-43395 alone or with fulvestrant or letrozole. Patients with HR-positive breast cancer generally must have received prior endocrine therapy and a CDK4/6 inhibitor where available, although a separate first-line, CDK4/6 inhibitor–naive cohort is included.
ClinicalTrials.gov ID: NCT06120283
