BGB-43395 Alone or as Part of Combination Therapies in Participants With 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 Patients With Metastatic HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

Overview

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.

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.

Interventions

• Drug BGB-43395
  Planned doses administered orally.
• Drug Fulvestrant
  Standard dose administered via intramuscular injection.
• Drug Letrozole
  Standard dose administered orally as a tablet.
• Drug Elacestrant
  Standard dose administered orally as a tablet.
• Drug Anti-Diarrheal Agent
  Administered orally as a tablet.

Primary outcome measures

• Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Up to approximately 60 months]
• Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395 [Time frame: Up to approximately 60 months]
• Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395 [Time frame: Up to approximately 60 months]
• Phase 1b: Objective Response Rate (ORR) [Time frame: Up to approximately 60 months]

Secondary outcome measures (12)

• Phase 1a: ORR [Time frame: Up to approximately 60 months]
• Phase 1a and 1b: Duration of Response (DOR) [Time frame: Up to approximately 60 months]
• Phase 1a and 1b: Time to Response (TTR) [Time frame: Up to approximately 60 months]
• Phase 1b: Disease Control Rate (DCR) [Time frame: Up to approximately 60 months]
• Phase 1b: Clinical Benefit Rate (CBR) [Time frame: Up to approximately 60 months]
• Phase 1b: Progression-Free Survival (PFS) [Time frame: Up to approximately 60 months]
• Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: Up to approximately 60 months]
• Phase 1a: Observed Plasma Maximum Concentration (Cmax) of BGB-43395 and its metabolite [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: From Cycle 1 Day 1 up to Cycle 5 Day 1 (each cycle is 28 days)]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Brazil · 11 centers

• Fundacao Pio Xii Hospital de Amor de Barretos — Barretos
• Hospital Sirio Libanes Brasilia — Brasília
• Centro de Pesquisas Oncologicas Cepon — Florianópolis
• Liga Norte Riograndene Contra O Cancer — Natal
• Fundacao Universidade de Caxias Do Sul Instituto de Pesquisas Em Saude — Petrópolis
• Hospital Sao Lucas Da Pucrs Uniao Brasileira de Educacao E Assistencia — Porto Algre
• Instituto Nacional de Cancer — Rio de Janeiro
• Instituto Dor de Pesquisa E Ensino Hospital Sao Rafael — Salvador
• … and 3 more centers

United States · 10 centers

• Sarah Cannon Research Institute (Scri) At Health One — Denver
• Florida Cancer Specialists and Research Institute — Lake Mary
• Karmanos Cancer Institute — Detroit
• Washington University School of Medicine — St Louis
• Duke Cancer Center — Durham
• James Cancer Hospital and Solove Research Institute — Columbus
• Scri Oncology Partners — Nashville
• The University of Texas Md Anderson Cancer Center — Houston
• … and 2 more centers

Australia · 8 centers

• Blacktown Cancer and Haematology Centre — Blacktown
• Southern Highlands Private Hospital — Bowral
• Concord Repatriation General Hospital — Concord
• Macquarie University — North Ryde
• Townsville University Hospital — Douglas
• Genesiscare St Andrews — Adelaide
• Austin Health — Heidelberg
• Peter Maccallum Cancer Centre — Melbourne

France · 8 centers

• Centre de Lutte Contre Le Cancer Institut Bergonie — Bordeaux
• Centre Francois Baclesse — Caen
• Centre Oscar Lambret — Lille
• Institut Paoli Calmettes — Marseille
• Institut Curie — Paris
• Centre Eugene Marquis — Rennes
• Institut de Cancerologie de Louest — Saint-Herblain
• Institut Gustave Roussy — Villejuif

South Korea · 8 centers

• Seoul National University Bundang Hospital — Seongnam-si
• Gachon University Gil Medical Center — NamdongGu
• Samsung Medical Center — GangnamGu
• The Catholic University of Korea, Seoul St Marys Hospital — SeochoGu
• Severance Hospital Yonsei University Health System — SeodaemunGu
• Korea University Anam Hospital — SeongbukGu
• Seoul National University Hospital — Seoul
• Asan Medical Center — SongpaGu

China · 7 centers

• Beijing Cancer Hospital — Beijing
• Fujian Cancer Hospital — Fuzhou
• Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South) — Guangzhou
• Harbin Medical University Cancer Hospital — Harbin
• The First Affiliated Hospital of Nanchang University Branch Donghu — Nanchang
• Liaoning Cancer Hospital and Institute — Shenyang
• Fudan University Shanghai Cancer Centerpudong — Shanghai

Malaysia · 4 centers

• Pulau Pinang Hospital — George Town
• University Malaya Medical Centre — Kuala Lumpur
• Sarawak General Hospital — Kuching
• National Cancer Institute (Institut Kanser Negara) — Putrajaya

Japan · 3 centers

• Nagoya University Hospital — Nagoya
• National Cancer Center Hospital East — Kashiwa
• Shizuoka Cancer Center — Suntogun

New Zealand · 2 centers

• Harbour Cancer and Wellness — Auckland
• Nzcr Christchurch — Christchurch

Moldova · 1 center

• The Institute of Oncology, Arensia Exploratory Medicine — Chisinau

Thailand · 1 center

• Srinagarind Hospital (Khon Kaen University) — Muang

Identifiers

NCT: NCT06120283 · BGB-43395-101 · 2023-506888-34-00 · CTR20243370

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)
• NMPA/CDE CTR20243370 (chinadrugtrials.org.cn platform)

View this study on ClinicalTrials.gov ↗