Advanced Solid TumorAdvanced Breast CancerMetastatic Breast CancerHormone-receptor-positive Breast CancerHormone Receptor Positive Breast CarcinomaHormone Receptor Positive Malignant Neoplasm of BreastHER2-negative Breast CancerHormone Receptor Positive HER-2 Negative Breast Cancer
Fulvestrant: Standard dose administered via intramuscular injection.
Letrozole: Standard dose administered orally as a tablet.
Elacestrant: Standard dose administered orally as a tablet.
Anti-Diarrheal Agent: Administered orally as a tablet.
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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. 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.
Primary outcome measure(s)
Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) — Up to approximately 60 months 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.
Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395 — Up to approximately 60 months 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.
Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395 — Up to approximately 60 months RDFE of BGB-43395 alone or in combination with fulvestrant, letrozole, or elacestrant will be determined based upon the MTD or MAD.
Phase 1b: Objective Response Rate (ORR) — Up to approximately 60 months 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.
Trial sites (62)
Facility
City
Region
Status
Sarah Cannon Research Institute (Scri) At Health One
Denver
Colorado
Recruiting
Florida Cancer Specialists and Research Institute
Lake Mary
Florida
Completed
Karmanos Cancer Institute
Detroit
Michigan
Completed
Washington University School of Medicine
St Louis
Missouri
Recruiting
Duke Cancer Center
Durham
North Carolina
Recruiting
James Cancer Hospital and Solove Research Institute
Columbus
Ohio
Recruiting
Scri Oncology Partners
Nashville
Tennessee
Recruiting
The University of Texas Md Anderson Cancer Center
Houston
Texas
Recruiting
Next Oncology Dallas
Irving
Texas
Recruiting
Next Oncology
San Antonio
Texas
Recruiting
Blacktown Cancer and Haematology Centre
Blacktown
New South Wales
Recruiting
Southern Highlands Private Hospital
Bowral
New South Wales
Recruiting
Concord Repatriation General Hospital
Concord
New South Wales
Recruiting
Macquarie University
North Ryde
New South Wales
Recruiting
Townsville University Hospital
Douglas
Queensland
Recruiting
Genesiscare St Andrews
Adelaide
South Australia
Recruiting
Austin Health
Heidelberg
Victoria
Completed
Peter Maccallum Cancer Centre
Melbourne
Victoria
Recruiting
Fundacao Pio Xii Hospital de Amor de Barretos
Barretos
Brazil
Recruiting
Hospital Sirio Libanes Brasilia
Brasília
Brazil
Recruiting
Centro de Pesquisas Oncologicas Cepon
Florianópolis
Brazil
Recruiting
Liga Norte Riograndene Contra O Cancer
Natal
Brazil
Recruiting
Fundacao Universidade de Caxias Do Sul Instituto de Pesquisas Em Saude
Petrópolis
Brazil
Recruiting
Hospital Sao Lucas Da Pucrs Uniao Brasileira de Educacao E Assistencia
Porto Algre
Brazil
Recruiting
Instituto Nacional de Cancer
Rio de Janeiro
Brazil
Recruiting
Instituto Dor de Pesquisa E Ensino Hospital Sao Rafael
Salvador
Brazil
Recruiting
Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
São Paulo
Brazil
Recruiting
Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E Mamaria
São Paulo
Brazil
Recruiting
Hospital Israelita Albert Einstein
São Paulo
Brazil
Recruiting
Beijing Cancer Hospital
Beijing
Beijing Municipality
Recruiting
Fujian Cancer Hospital
Fuzhou
Fujian
Recruiting
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
Guangzhou
Guangdong
Recruiting
Harbin Medical University Cancer Hospital
Harbin
Heilongjiang
Recruiting
The First Affiliated Hospital of Nanchang University Branch Donghu
Nanchang
Jiangxi
Recruiting
Liaoning Cancer Hospital and Institute
Shenyang
Liaoning
Recruiting
Fudan University Shanghai Cancer Centerpudong
Shanghai
Shanghai Municipality
Recruiting
Centre de Lutte Contre Le Cancer Institut Bergonie
Bordeaux
France
Recruiting
Centre Francois Baclesse
Caen
France
Recruiting
Centre Oscar Lambret
Lille
France
Recruiting
Institut Paoli Calmettes
Marseille
France
Recruiting
+ 22 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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