BGB-43395 Alone or as Part of Combination Therapies in Participants With Breast Cancer and Other Advanced Solid Tumors
- Conditions
- Advanced Solid TumorHormone Receptor Positive Malignant Neoplasm of BreastAdvanced Breast CancerMetastatic Breast CancerHormone-receptor-positive Breast CancerHER2-negative Breast CancerHormone Receptor Positive HER-2 Negative Breast CancerNon-small Cell Lung CancerHormone Receptor Positive Breast Carcinoma
- Interventions
- Registration Number
- NCT06120283
- Lead Sponsor
- BeiGene
- Brief Summary
This is a dose escalation and dose expansion study to compare how well BGB-43395, a cyclin-dependent kinase 4 (CDK4) inhibitor, works as monotherapy or in combination with either fulvestrant or letrozole 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
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 79
- Phase 1a (Dose Escalation) and 1b (Dose Expansion): 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.
- Phase 1a: Received prior therapy for their condition (if available) and should be refractory to or intolerant of standard-of-care therapies. In regions where approved and available, participants with HR+ breast cancer must have received at least 2 prior lines of treatment including endocrine therapy and a CDK4/6 inhibitor.
- Phase 1b: Selected tumor cohorts will include HR+/HER2- breast cancer and additional tumor types.
- Phase 1b: Participants with HR+/HER2- breast cancer enrolled in regions where CDK4/6 inhibitors are approved and available must have received at least one line of therapy for advanced disease including endocrine therapy and a CDK4/6 inhibitor. Participants can have received up to 2 lines of prior cytotoxic chemotherapy 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.
- Prior therapy selectively targeting CDK4 (prior CDK4/6 inhibitor therapy is permitted and required in local regions where it is approved and available).
- 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.
- History of hepatitis B or active hepatitis C infection.
- Prior allogeneic stem cell transplantation, or organ transplantation.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Dose Escalation BGB-43395 Phase 1a: Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole to assess for safety and tolerability. Dose Escalation Fulvestrant Phase 1a: Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole to assess for safety and tolerability. Dose Escalation Letrozole Phase 1a: Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole to assess for safety and tolerability. Dose Expansion Fulvestrant Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant or letrozole) from Phase 1a will be evaluated in HR+ breast cancer and selected tumor-specific cohorts. Dose Expansion Letrozole Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant or letrozole) from Phase 1a will be evaluated in HR+ breast cancer and selected tumor-specific cohorts. Dose Expansion BGB-43395 Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant or letrozole) from Phase 1a will be evaluated in HR+ breast cancer and selected tumor-specific cohorts.
- Primary Outcome Measures
Name Time Method 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.
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 or letrozole will be determined based upon the MTD or MAD.
- Secondary Outcome Measures
Name Time Method Phase 1a: ORR Up to approximately 60 months ORR is defined as the percentage of participants who have confirmed CR or PR assessed by the investigator using RECIST v1.1.
Phase 1b: Progression-Free Survival (PFS) Up to approximately 60 months 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.
Phase 1a and 1b: Duration of Response (DOR) Up to approximately 60 months 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.
Phase 1a and 1b: Time to Response (TTR) Up to approximately 60 months 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.
Phase 1b: Disease Control Rate (DCR) Up to approximately 60 months 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.
Phase 1b: Clinical Benefit Rate (CBR) Up to approximately 60 months CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting ≥ 24 weeks.
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 1b: 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), and laboratory assessments.
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)
Trial Locations
- Locations (127)
Fundacao Universidade de Caxias Do Sul Instituto de Pesquisas Em Saude
🇧🇷Petropolis, Brazil
Hospital Sao Lucas Da Pucrs Uniao Brasileira de Educacao E Assistencia
🇧🇷Porto Algre, Brazil
Sarah Cannon Research Institute (Scri) At Health One
🇺🇸Denver, Colorado, United States
Florida Cancer Specialists and Research Institute
🇺🇸Lake Mary, Florida, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Scri Oncology Partners
🇺🇸Nashville, Tennessee, United States
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Next Dallas
🇺🇸Irving, Texas, United States
Next Oncology
🇺🇸San Antonio, Texas, United States
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Southern Highlands Private Hospital
🇦🇺Bowral, New South Wales, Australia
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Macquarie University
🇦🇺North Ryde, New South Wales, Australia
Townsville University Hospital
🇦🇺Douglas, Queensland, Australia
Genesiscare St Andrews
🇦🇺Adelaide, South Australia, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Fundacao Pio Xii Hospital de Amor de Barretos
🇧🇷Barretos, Brazil
Hospital Sirio Libanes Brasilia
🇧🇷Brasilia, Brazil
Centro de Pesquisas Oncologicas Cepon
🇧🇷Florianopolis, Brazil
Liga Norte Riograndene Contra O Cancer
🇧🇷Natal, Brazil
Instituto Nacional de Cancer
🇧🇷Rio de Janeiro, Brazil
Instituto Dor de Pesquisa E Ensino Hospital Sao Rafael
🇧🇷Salvador, Brazil
Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
🇧🇷Sao Paulo, Brazil
Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E Mamaria
🇧🇷Sao Paulo, Brazil
Hospital Israelita Albert Einstein
🇧🇷Sao Paulo, Brazil
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Liaoning Cancer Hospital and Institute
🇨🇳Shenyang, Liaoning, China
Fudan University Shanghai Cancer Centerpudong
🇨🇳Shanghai, Shanghai, China
Centre de Lutte Contre Le Cancer Institut Bergonie
🇫🇷Bordeaux, France
Centre Francois Baclesse
🇫🇷Caen, France
Centre Oscar Lambret
🇫🇷Lille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Institut Curie
🇫🇷Paris, France
Centre Eugene Marquis
🇫🇷Rennes, France
Institut de Cancerologie de Louest
🇫🇷St Herblain, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Shizuoka Cancer Center
🇯🇵Suntogun, Shizuoka, Japan
Seoul National University Bundang Hospital
🇰🇷BundangGu SeongnamSi, Gyeonggi-do, Korea, Republic of
Korea University Anam Hospital
🇰🇷SeongbukGu, Gyeonggi-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷NamdongGu, Incheon Gwang'yeogsi, Korea, Republic of
Samsung Medical Center
🇰🇷GangnamGu, Seoul Teugbyeolsi, Korea, Republic of
The Catholic University of Korea, Seoul St Marys Hospital
🇰🇷SeochoGu, Seoul Teugbyeolsi, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷SeodaemunGu, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center
🇰🇷SongpaGu, Seoul Teugbyeolsi, Korea, Republic of
Pulau Pinang Hospital
🇲🇾Georgetown, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Sarawak General Hospital
🇲🇾Kuching, Malaysia
National Cancer Institute (Institut Kanser Negara)
🇲🇾Putrajaya, Malaysia
The Institute of Oncology, Arensia Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
Harbour Cancer and Wellness
🇳🇿Auckland, New Zealand
Nzcr Christchurch
🇳🇿Christchurch, New Zealand
Siriraj Hospital
🇹🇭Bangkok, Thailand
Srinagarind Hospital (Khon Kaen University)
🇹🇭Muang, Thailand
Liga Norte Riograndene Contra O Cancer
🇧🇷Natal, Brazil
Sarah Cannon Research Institute (Scri) At Health One
🇺🇸Denver, Colorado, United States
Florida Cancer Specialists and Research Institute
🇺🇸Lake Mary, Florida, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Genesiscare St Andrews
🇦🇺Adelaide, South Australia, Australia
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Duke Cancer Center
🇺🇸Durham, North Carolina, United States
James Cancer Hospital and Solove Research Institute
🇺🇸Columbus, Ohio, United States
Scri Oncology Partners
🇺🇸Nashville, Tennessee, United States
The University of Texas Md Anderson Cancer Center
🇺🇸Houston, Texas, United States
Next Dallas
🇺🇸Irving, Texas, United States
Next Oncology
🇺🇸San Antonio, Texas, United States
Blacktown Cancer and Haematology Centre
🇦🇺Blacktown, New South Wales, Australia
Southern Highlands Private Hospital
🇦🇺Bowral, New South Wales, Australia
Concord Repatriation General Hospital
🇦🇺Concord, New South Wales, Australia
Macquarie University
🇦🇺North Ryde, New South Wales, Australia
Townsville University Hospital
🇦🇺Douglas, Queensland, Australia
Austin Health
🇦🇺Heidelberg, Victoria, Australia
Peter Maccallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
Fundacao Pio Xii Hospital de Amor de Barretos
🇧🇷Barretos, Brazil
Hospital Sirio Libanes Brasilia
🇧🇷Brasilia, Brazil
Centro de Pesquisas Oncologicas Cepon
🇧🇷Florianopolis, Brazil
Fundacao Universidade de Caxias Do Sul Instituto de Pesquisas Em Saude
🇧🇷Petropolis, Brazil
Hospital Sao Lucas Da Pucrs Uniao Brasileira de Educacao E Assistencia
🇧🇷Porto Algre, Brazil
Instituto Nacional de Cancer
🇧🇷Rio de Janeiro, Brazil
Instituto Dor de Pesquisa E Ensino Hospital Sao Rafael
🇧🇷Salvador, Brazil
Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
🇧🇷Sao Paulo, Brazil
Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E Mamaria
🇧🇷Sao Paulo, Brazil
Hospital Israelita Albert Einstein
🇧🇷Sao Paulo, Brazil
Beijing Cancer Hospital
🇨🇳Beijing, Beijing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
🇨🇳Guangzhou, Guangdong, China
Harbin Medical University Cancer Hospital
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Nanchang University Branch Donghu
🇨🇳Nanchang, Jiangxi, China
Liaoning Cancer Hospital and Institute
🇨🇳Shenyang, Liaoning, China
Fudan University Shanghai Cancer Centerpudong
🇨🇳Shanghai, Shanghai, China
Centre de Lutte Contre Le Cancer Institut Bergonie
🇫🇷Bordeaux, France
Centre Francois Baclesse
🇫🇷Caen, France
Centre Oscar Lambret
🇫🇷Lille, France
Institut Paoli Calmettes
🇫🇷Marseille, France
Institut Curie
🇫🇷Paris, France
Centre Eugene Marquis
🇫🇷Rennes, France
Institut de Cancerologie de Louest
🇫🇷St Herblain, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Shizuoka Cancer Center
🇯🇵Suntogun, Shizuoka, Japan
Seoul National University Bundang Hospital
🇰🇷BundangGu SeongnamSi, Gyeonggi-do, Korea, Republic of
Korea University Anam Hospital
🇰🇷SeongbukGu, Gyeonggi-do, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷NamdongGu, Incheon Gwang'yeogsi, Korea, Republic of
Samsung Medical Center
🇰🇷GangnamGu, Seoul Teugbyeolsi, Korea, Republic of
The Catholic University of Korea, Seoul St Marys Hospital
🇰🇷SeochoGu, Seoul Teugbyeolsi, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷SeodaemunGu, Seoul Teugbyeolsi, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul Teugbyeolsi, Korea, Republic of
Asan Medical Center
🇰🇷SongpaGu, Seoul Teugbyeolsi, Korea, Republic of
Pulau Pinang Hospital
🇲🇾Georgetown, Malaysia
University Malaya Medical Centre
🇲🇾Kuala Lumpur, Malaysia
Sarawak General Hospital
🇲🇾Kuching, Malaysia
National Cancer Institute (Institut Kanser Negara)
🇲🇾Putrajaya, Malaysia
The Institute of Oncology, Arensia Exploratory Medicine
🇲🇩Chisinau, Moldova, Republic of
Harbour Cancer and Wellness
🇳🇿Auckland, New Zealand
Nzcr Christchurch
🇳🇿Christchurch, New Zealand
Srinagarind Hospital (Khon Kaen University)
🇹🇭Muang, Thailand