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

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 Patients With Metastatic HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

This is a dose escalation and dose expansion study to compare how well BGB-43395, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, works as monotherapy or in combination with fulvestrant, letrozole, or elacestrant in participants with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer (BC) and other advanced solid tumors. The main purpose of this study is to explore the recommended dosing for BGB-43395.

Study Overview

• Status: Recruiting
• Conditions: Advanced Breast Cancer; Metastatic Breast Cancer; Advanced Solid Tumor; Non-small Cell Lung Cancer; Hormone Receptor Positive Malignant Neoplasm of Breast; Hormone Receptor Positive Breast Carcinoma; HER2-negative Breast Cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer; Hormone-receptor-positive Breast Cancer
• Intervention / Treatment: Drug: BGB-43395; Drug: Fulvestrant; Drug: Letrozole; Drug: Elacestrant; Drug: Anti-Diarrheal Agent

Detailed Description

Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.

• Study Type: Interventional
• Enrollment (Estimated): 399
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Director; Phone Number: 1.877.828.5568; Email: clinicaltrials@beonemed.com

Study Locations

• Australia
  • New South Wales
    • Blacktown, New South Wales, Australia, NSW 2148
      • Recruiting
      • Blacktown Cancer and Haematology Centre
    • Bowral, New South Wales, Australia, NSW 2576
      • Recruiting
      • Southern Highlands Private Hospital
    • Concord, New South Wales, Australia, NSW 2139
      • Recruiting
      • Concord Repatriation General Hospital
    • North Ryde, New South Wales, Australia, NSW 2109
      • Recruiting
      • Macquarie University
  • Queensland
    • Douglas, Queensland, Australia, QLD 4814
      • Recruiting
      • Townsville University Hospital
  • South Australia
    • Adelaide, South Australia, Australia, SA 5000
      • Recruiting
      • Genesiscare St Andrews
  • Victoria
    • Heidelberg, Victoria, Australia, VIC 3084
      • Recruiting
      • Austin Health
    • Melbourne, Victoria, Australia, VIC 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
• Brazil
  • Barretos, Brazil, 14.784-400
    • Recruiting
    • Fundacao Pio Xii Hospital de Amor de Barretos
  • Brasília, Brazil, 70200-730
    • Recruiting
    • Hospital Sirio Libanes Brasilia
  • Florianópolis, Brazil, 88034-000
    • Recruiting
    • Centro de Pesquisas Oncologicas Cepon
  • Natal, Brazil, 59062-000
    • Recruiting
    • Liga Norte Riograndene Contra O Cancer
  • Petrópolis, Brazil, 95070-560
    • Recruiting
    • Fundacao Universidade de Caxias Do Sul Instituto de Pesquisas Em Saude
  • Porto Algre, Brazil, 90610-000
    • Recruiting
    • Hospital Sao Lucas Da Pucrs Uniao Brasileira de Educacao E Assistencia
  • Rio de Janeiro, Brazil, 20560-120
    • Recruiting
    • Instituto Nacional de Cancer
  • Salvador, Brazil, 41253-190
    • Recruiting
    • Instituto Dor de Pesquisa E Ensino Hospital Sao Rafael
  • São Paulo, Brazil, 05652-900
    • Recruiting
    • Hospital Israelita Albert Einstein
  • São Paulo, Brazil, 01246-000
    • Recruiting
    • Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
  • São Paulo, Brazil, 01318-001
    • Recruiting
    • Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E Mamaria
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100142
      • Recruiting
      • Beijing Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Recruiting
      • Fujian Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510245
      • Recruiting
      • Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Recruiting
      • The First Affiliated Hospital of Nanchang University Branch Donghu
  • Liaoning
    • Shenyang, Liaoning, China, 110042
      • Recruiting
      • Liaoning Cancer Hospital and Institute
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 201321
      • Recruiting
      • Fudan University Shanghai Cancer Centerpudong
• France
  • Bordeaux, France, 33000
    • Recruiting
    • Centre de Lutte Contre Le Cancer Institut Bergonie
  • Caen, France, 14000
    • Recruiting
    • Centre Francois Baclesse
  • Lille, France, 59000
    • Recruiting
    • Centre Oscar Lambret
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
  • Paris, France, 75005
    • Recruiting
    • Institut Curie
  • Rennes, France, 35043
    • Recruiting
    • Centre Eugène Marquis
  • Saint-Herblain, France, 44800
    • Recruiting
    • Institut de Cancerologie de Louest
  • Villejuif, France, 94800
    • Recruiting
    • Institut Gustave Roussy
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 466-8560
      • Recruiting
      • Nagoya University Hospital
  • Chiba
    • Kashiwa, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Shizuoka
    • Suntogun, Shizuoka, Japan, 411-8777
      • Recruiting
      • Shizuoka Cancer Center
• Malaysia
  • George Town, Malaysia, 10450
    • Recruiting
    • Pulau Pinang Hospital
  • Kuala Lumpur, Malaysia, 59100
    • Recruiting
    • University Malaya Medical Centre
  • Kuching, Malaysia, 93586
    • Recruiting
    • Sarawak General Hospital
  • Putrajaya, Malaysia, 62250
    • Recruiting
    • National Cancer Institute (Institut Kanser Negara)
• Moldova
  • Chisinau, Moldova, 2025
    • Active, not recruiting
    • The Institute of Oncology, Arensia Exploratory Medicine
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Harbour Cancer and Wellness
  • Christchurch, New Zealand, 8011
    • Recruiting
    • Nzcr Christchurch
• South Korea
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, South Korea, 13620
      • Recruiting
      • Seoul National University Bundang Hospital
  • Incheon Gwang'yeogsi
    • NamdongGu, Incheon Gwang'yeogsi, South Korea, 21565
      • Recruiting
      • Gachon University Gil Medical Center
  • Seoul Teugbyeolsi
    • GangnamGu, Seoul Teugbyeolsi, South Korea, 06351
      • Recruiting
      • Samsung Medical Center
    • SeochoGu, Seoul Teugbyeolsi, South Korea, 06591
      • Recruiting
      • The Catholic University of Korea, Seoul St Marys Hospital
    • SeodaemunGu, Seoul Teugbyeolsi, South Korea, 03722
      • Recruiting
      • Severance Hospital Yonsei University Health System
    • SeongbukGu, Seoul Teugbyeolsi, South Korea, 02841
      • Recruiting
      • Korea University Anam Hospital
    • Seoul, Seoul Teugbyeolsi, South Korea, 03080
      • Recruiting
      • Seoul National University Hospital
    • SongpaGu, Seoul Teugbyeolsi, South Korea, 05505
      • Recruiting
      • Asan Medical Center
• Thailand
  • Muang, Thailand, 40002
    • Active, not recruiting
    • Srinagarind Hospital (Khon Kaen University)
• United States
  • Colorado
    • Denver, Colorado, United States, 80218-1238
      • Recruiting
      • Sarah Cannon Research Institute (Scri) At Health One
  • Florida
    • Lake Mary, Florida, United States, 32746-2115
      • Completed
      • Florida Cancer Specialists and Research Institute
  • Michigan
    • Detroit, Michigan, United States, 48201-2013
      • Completed
      • Karmanos Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Recruiting
      • Washington University School of Medicine
  • North Carolina
    • Durham, North Carolina, United States, 27710-2000
      • Recruiting
      • Duke Cancer Center
  • Ohio
    • Columbus, Ohio, United States, 43210-1240
      • Recruiting
      • James Cancer Hospital and Solove Research Institute
  • Tennessee
    • Nashville, Tennessee, United States, 37203-1503
      • Recruiting
      • SCRI Oncology Partners
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
    • Irving, Texas, United States, 75039-2743
      • Recruiting
      • Next Dallas
    • San Antonio, Texas, United States, 78229-6028
      • Recruiting
      • NEXT Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Phase 1a (Dose Escalation): Participants with histologically or cytologically confirmed advanced, metastatic, or unresectable solid tumors associated with dependency on CDK4, including HR+ breast cancer, ovarian cancer, endometrial cancer, non-small cell lung cancer, and others. For combination with elacestrant, participants must have received at least 1 prior line of treatment for advanced/metastatic disease including prior endocrine therapy and CDK4/6 inhibitor in either the adjuvant or advanced/metastatic setting.
• Phase 1a Safety Expansion: For combination with fulvestrant in regions where approved and available, participants with HR+ breast cancer must have received at least 1 prior line of treatment including endocrine therapy and a CDK4/6 inhibitor. For combination with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease.
• Phase 1b: Participants with HR+/HER2- breast cancer.
• Phase 1b: For combination with fulvestrant, participants with HR+/HER2- breast cancer enrolled in regions where CDK4/6 inhibitors are approved and available must have received 1-2 lines of therapy for advanced/metastatic disease including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy for advanced disease. Prior cytotoxic treatment is prohibited. For combination cohorts with letrozole, participants must be CDK4/6 inhibitor treatment naïve and have not received any previous systemic treatment for advanced disease.
• Stable Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Female participants with metastatic HR+/HER2- breast cancer must be postmenopausal or receiving ovarian function suppression treatment.
• Adequate organ function without symptomatic visceral disease.

Exclusion Criteria:

• Known leptomeningeal disease or uncontrolled, untreated brain metastases.
• Any malignancy ≤ 3 years before the first dose of study treatment(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.
• Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL (or ≥ 2500 copies/mL) at screening.
• Participants with active hepatitis C infection.
• Prior allogeneic stem cell transplantation, or organ transplantation.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation; Phase 1a: Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant, letrozole, or elacestrant to assess for safety and tolerability.	Drug: BGB-43395; Planned doses administered orally.; Drug: Fulvestrant; Standard dose administered via intramuscular injection.; Other Names: Faslodex®; Drug: Letrozole; Standard dose administered orally as a tablet.; Other Names: Femara®; Drug: Elacestrant; Standard dose administered orally as a tablet.
Experimental: Safety Expansion; Phase 1a: Cohorts of selected dose levels of BGB-43395 in combination with fulvestrant or letrozole in HR+/HER2 breast cancer.	Drug: BGB-43395; Planned doses administered orally.; Drug: Fulvestrant; Standard dose administered via intramuscular injection.; Other Names: Faslodex®; Drug: Letrozole; Standard dose administered orally as a tablet.; Other Names: Femara®
Experimental: Dose Expansion Cohort 1; Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant) from Phase 1a will be evaluated in HR+ breast cancer.	Drug: BGB-43395; Planned doses administered orally.; Drug: Fulvestrant; Standard dose administered via intramuscular injection.; Other Names: Faslodex®
Experimental: Dose Expansion Cohort 2; Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 in combination with letrozole from Phase 1a will be evaluated in HR+ breast cancer.	Drug: BGB-43395; Planned doses administered orally.; Drug: Letrozole; Standard dose administered orally as a tablet.; Other Names: Femara®
Experimental: Dose Expansion Cohort 3; Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 in combination with letrozole from Phase 1a will be evaluated in HR+ breast cancer. Participants will also receive an anti-diarrheal agent for prophylaxis.	Drug: BGB-43395; Planned doses administered orally.; Drug: Letrozole; Standard dose administered orally as a tablet.; Other Names: Femara®; Drug: Anti-Diarrheal Agent; Administered orally as a tablet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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), laboratory assessments, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.	Up to approximately 60 months
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 of 28%. MAD is defined as the highest dose administered if MTD is not reached.	Up to approximately 60 months
Phase 1b: Objective Response Rate (ORR)	ORR is defined as the percentage of participants who have confirmed complete response (CR) or partial response (PR) assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.	Up to approximately 60 months
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395	RDFE of BGB-43395 alone or in combination with fulvestrant, letrozole, or elacestrant will be determined based upon the MTD or MAD.	Up to approximately 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)
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 60 months
Phase 1a and 1b: Duration of Response (DOR)	DOR is defined as the time from the first determination of an overall response per RECIST v1.1 until the first documentation of disease progression or death, whichever occurs first as assessed by the investigator.	Up to approximately 60 months
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 by the investigator using RECIST v1.1.	Up to approximately 60 months
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 60 months
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 60 months
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 60 months
Phase 1b: 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.	Up to approximately 60 months

Collaborators and Investigators

• Sponsor: BeOne Medicines
• Investigators: Study Director: Study Director, BeOne Medicines

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2023
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: November 1, 2023
• First Submitted That Met QC Criteria: November 1, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): April 15, 2026
• Last Update Submitted That Met QC Criteria: April 10, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; non-small cell lung cancer; advanced solid tumor; advanced breast cancer; HER2-negative breast cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer; hormone receptor positive breast cancer; BGB-43395
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Skin Diseases; Breast Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Skin and Connective Tissue Diseases; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Nitriles; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Triazoles; Letrozole; Fulvestrant; elacestrant
• Other Study ID Numbers: BGB-43395-101; 2023-506888-34-00 (Registry Identifier: EU CTIS); CTR20243370 (Registry Identifier: ChinaDrugTrials.org)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

BeOne shares data on completed studies responsibly and provides qualified scientific and medical researchers access to data and supporting documentation for clinical trials in dossiers for medicines and indications after submission and approval in the United States, China, and Europe. Clinical trials supporting subsequent local approvals, new indications, or combination products are eligible for sharing once corresponding regulatory approvals are achieved.

BeOne shares data only when permitted by applicable data privacy and security laws and regulations, when it is feasible to do so without compromising the privacy of study participants, and other considerations.

Qualified researchers with appropriate competencies who are engaged in novel scientific research may submit a request for participant-level data with a research proposal for BeOne review. Research teams must include a biostatistician and sign a Data Sharing Agreement prior to receiving access to clinical trial data.

• IPD Sharing Time Frame: See plan description
• IPD Sharing Access Criteria: See plan description
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No