Investigational Drug
BGB-43395
HealthScout AI Analysis
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Overview
BGB-43395 is an orally administered, highly selective cyclin-dependent kinase 4 (CDK4) inhibitor under development by BeiGene for HR+/HER2− breast cancer and other advanced solid tumors. Phase 1a/1b studies are ongoing globally (NCT06120283) and in China (NCT06253195), with monotherapy and combinations with endocrine therapy (e.g., fulvestrant, letrozole, elacestrant). A healthy-volunteer formulation/food‑effect study is also underway (NCT06761898). (cdek.pharmacy.purdue.edu)
Mechanism of action
BGB-43395 selectively inhibits CDK4, a key regulator of G1–S cell‑cycle transition via phosphorylation of the retinoblastoma (Rb) protein. Selective CDK4 inhibition is being explored to maintain antitumor activity while potentially reducing CDK6‑related myelosuppression seen with dual CDK4/6 inhibitors. Company communications around SABCS 2024 described BGB-43395 as “highly potent and selective for CDK4 relative to CDK6.” (ir.beigene.com)
Clinical development status
- Global first‑in‑human Phase 1a/1b (NCT06120283): dose escalation and expansion assessing BGB-43395 as monotherapy and with fulvestrant or letrozole in metastatic HR+/HER2− breast cancer and selected solid tumors; multiple U.S. academic sites list the trial as open. (cdek.pharmacy.purdue.edu)
- China Phase 1a/1b (NCT06253195): similar design in Chinese participants; active, not recruiting as of June 2025 (primary completion estimated February 2026). (cdek.pharmacy.purdue.edu)
- Healthy‑volunteer PK/formulation study (NCT06761898): evaluates relative bioavailability and food effect in the U.S. (trial.medpath.com)
- BeiGene has indicated continued dose escalation/expansion with planning for a Phase 3 study in second‑line HR+/HER2− metastatic breast cancer in combination with endocrine therapy. (ir.beigene.com)
Efficacy
As of the latest public updates (through August 2025), detailed response data (e.g., ORR) from human studies have not been posted on trial registries or published in peer‑reviewed venues. Company reports following SABCS 2024 noted “encouraging early signs of clinical activity” without quantitative outcomes disclosed. (cdek.pharmacy.purdue.edu)
Safety
No peer‑reviewed, detailed human safety dataset has been published yet. Early, high‑level company communications from SABCS 2024 described BGB-43395 as “generally well tolerated” across dose levels in the first‑in‑human study; full adverse‑event rates were not provided. The development rationale emphasizes CDK4 selectivity to potentially mitigate CDK6‑associated neutropenia seen with approved CDK4/6 inhibitors. (ir.beigene.com)
Further reading
- Global Phase 1a/1b (NCT06120283) trial listing/summary (CDEK) and U.S. site pages (Duke; MD Anderson). (cdek.pharmacy.purdue.edu)
- China Phase 1a/1b (NCT06253195) trial listing/summary (CDEK/MedPath/ICH GCP). (cdek.pharmacy.purdue.edu)
- Healthy‑volunteer formulation/food‑effect study (NCT06761898) overview (MedPath). (trial.medpath.com)
- BeiGene SABCS 2024 announcement summarizing first‑in‑human presentations for BGB-43395. (ir.beigene.com)
- BeiGene 4Q24/Full‑year update outlining program status and Phase 3 planning. (ir.beigene.com)
Note: The SABCS 2024 abstracts were published in a Clinical Cancer Research supplement; however, as of this writing, a BGB‑43395 abstract with quantitative efficacy/safety data could not be retrieved from the public supplement index. (sabcs.org)
Last updated: Oct 2025
Active trials using BGB-43395
Found 3 active trials using this drug:
HealthScout AI summary: Eligible patients are adults with HR+/HER2- metastatic breast cancer who have progressed on at least two prior lines of therapy (including both endocrine therapy and a CDK4/6 inhibitor) and will receive BGB-21447, a selective oral Bcl-2 inhibitor, in combination with fulvestrant with or without the investigational oral CDK4 inhibitor BGB-43395. Both postmenopausal women and men with good performance status and adequate organ function may enroll.
ClinicalTrials.gov ID: NCT06756932
HealthScout AI summary: This trial enrolls adults with advanced, nonresectable, or metastatic solid tumors—including HR+/HER2- breast cancer, platinum-resistant serous ovarian, endometrial, and other tumors with likely CDK2 dependency—who have progressed on standard therapies. Patients receive the investigational selective CDK2 inhibitor BG-68501 as monotherapy or in combination with fulvestrant, with HR+/HER2- breast cancer patients also eligible for a triple combination with fulvestrant and the selective CDK4 inhibitor BGB-43395.
ClinicalTrials.gov ID: NCT06257264
HealthScout AI summary: This trial enrolls adults with metastatic HR+/HER2- breast cancer and other advanced solid tumors likely dependent on CDK4 activity, who have progressed on or are intolerant to standard therapies, to receive the investigational CDK4 inhibitor BGB-43395 (a selective CDK4 inhibitor with minimal CDK6 inhibition) as monotherapy or combined with fulvestrant or letrozole. Prior CDK4/6 inhibitor exposure is permitted and sometimes required, but prior selective CDK4 inhibitors are excluded.
ClinicalTrials.gov ID: NCT06120283
