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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Бразилия · 11 центров

• 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
• … и ещё 3 центра

США · 10 центров

• 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
• … и ещё 2 центра

Австралия · 8 центров

• 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

Франция · 8 центров

• 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 центров

• 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

Китай · 7 центров

• Beijing Cancer Hospital — Пекин
• Fujian Cancer Hospital — Фучжоу
• Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South) — Гуанчжоу
• Harbin Medical University Cancer Hospital — Харбин
• The First Affiliated Hospital of Nanchang University Branch Donghu — Nanchang
• Liaoning Cancer Hospital and Institute — Шэньян
• Fudan University Shanghai Cancer Centerpudong — Шанхай

Малайзия · 4 центра

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

Япония · 3 центра

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

Новая Зеландия · 2 центра

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

Moldova · 1 центр

• The Institute of Oncology, Arensia Exploratory Medicine — Chisinau

Таиланд · 1 центр

• Srinagarind Hospital (Khon Kaen University) — Muang

Идентификаторы

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

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)
• NMPA/CDE CTR20243370 (платформа chinadrugtrials.org.cn)

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