Clinical trial NCT06120283: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumor
Advanced Breast Cancer
Metastatic Breast Cancer
Hormone-receptor-positive Breast Cancer
Hormone Receptor Positive Breast Carcinoma
Hormone Receptor Positive Malignant Neoplasm of Breast
HER2-negative Breast Cancer
Hormone Receptor Positive HER-2 Negative Breast Cancer
Non-small Cell Lung Cancer
Keywords: breast cancer
advanced solid tumor
advanced breast cancer
hormone receptor positive breast cancer
HER2-negative breast cancer
Hormone Receptor Positive HER-2 Negative Breast Cancer
BGB-43395
non-small cell lung cancer
Lead sponsor: BeiGene
Sponsor class: INDUSTRY
First posted: 2023-11-07
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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 criteria: Inclusion Criteria:

* 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. 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 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.

Exclusion Criteria:

* 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.
* 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 outcomes:
measure: Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 60 months
measure: Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395
timeFrame: Up to approximately 60 months
measure: Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395
timeFrame: Up to approximately 60 months
measure: Phase 1b: Objective Response Rate (ORR)
timeFrame: Up to approximately 60 months
Secondary outcomes:
measure: Phase 1a: ORR
timeFrame: Up to approximately 60 months
measure: Phase 1a and 1b: Duration of Response (DOR)
timeFrame: Up to approximately 60 months
measure: Phase 1a and 1b: Time to Response (TTR)
timeFrame: Up to approximately 60 months
measure: Phase 1b: Disease Control Rate (DCR)
timeFrame: Up to approximately 60 months
measure: Phase 1b: Clinical Benefit Rate (CBR)
timeFrame: Up to approximately 60 months
measure: Phase 1b: Progression-Free Survival (PFS)
timeFrame: Up to approximately 60 months
measure: Phase 1b: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to approximately 60 months
measure: Phase 1a: Observed Plasma Maximum Concentration (Cmax) of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
measure: Phase 1a: Observed Plasma Trough Concentration (Ctrough) of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
measure: Phase 1a: Area under the concentration-time curve (AUC) of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
measure: Phase 1a: Half-life (t1/2) of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 7 Day 1 (each cycle is 28 days)
measure: Phase 1b: Plasma concentrations of BGB-43395 and its metabolite
timeFrame: From Cycle 1 Day 1 up to Cycle 5 Day 1 (each cycle is 28 days)
Other outcomes:
Locations:
city: Denver
country: United States
facility: Sarah Cannon Research Institute (Scri) At Health One
state: Colorado
city: Lake Mary
country: United States
facility: Florida Cancer Specialists and Research Institute
state: Florida
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Durham
country: United States
facility: Duke Cancer Center
state: North Carolina
city: Columbus
country: United States
facility: James Cancer Hospital and Solove Research Institute
state: Ohio
city: Nashville
country: United States
facility: Scri Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: The University of Texas Md Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: Next Dallas
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Blacktown
country: Australia
facility: Blacktown Cancer and Haematology Centre
state: New South Wales
city: Bowral
country: Australia
facility: Southern Highlands Private Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: North Ryde
country: Australia
facility: Macquarie University
state: New South Wales
city: Douglas
country: Australia
facility: Townsville University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Genesiscare St Andrews
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Melbourne
country: Australia
facility: Peter Maccallum Cancer Centre
state: Victoria
city: Barretos
country: Brazil
facility: Fundacao Pio Xii Hospital de Amor de Barretos
city: Brasilia
country: Brazil
facility: Hospital Sirio Libanes Brasilia
city: Florianopolis
country: Brazil
facility: Centro de Pesquisas Oncologicas Cepon
city: Natal
country: Brazil
facility: Liga Norte Riograndene Contra O Cancer
city: Petropolis
country: Brazil
facility: Fundacao Universidade de Caxias Do Sul Instituto de Pesquisas Em Saude
city: Porto Algre
country: Brazil
facility: Hospital Sao Lucas Da Pucrs Uniao Brasileira de Educacao E Assistencia
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer
city: Salvador
country: Brazil
facility: Instituto Dor de Pesquisa E Ensino Hospital Sao Rafael
city: Sao Paulo
country: Brazil
facility: Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira
city: Sao Paulo
country: Brazil
facility: Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E Mamaria
city: Sao Paulo
country: Brazil
facility: Hospital Israelita Albert Einstein
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Guangzhou
country: China
facility: Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)
state: Guangdong
city: Harbin
country: China
facility: Harbin Medical University Cancer Hospital
state: Heilongjiang
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University Branch Donghu
state: Jiangxi
city: Shenyang
country: China
facility: Liaoning Cancer Hospital and Institute
state: Liaoning
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Centerpudong
state: Shanghai
city: Bordeaux
country: France
facility: Centre de Lutte Contre Le Cancer Institut Bergonie
city: Caen
country: France
facility: Centre Francois Baclesse
city: Lille
country: France
facility: Centre Oscar Lambret
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Paris
country: France
facility: Institut Curie
city: Rennes
country: France
facility: Centre Eugene Marquis
city: St Herblain
country: France
facility: Institut de Cancerologie de Louest
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Suntogun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: BundangGu SeongnamSi
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: SeongbukGu
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Gyeonggi-do
city: NamdongGu
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Incheon Gwang'yeogsi
city: GangnamGu
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul Teugbyeolsi
city: SeochoGu
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St Marys Hospital
state: Seoul Teugbyeolsi
city: SeodaemunGu
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul Teugbyeolsi
city: SongpaGu
country: Korea, Republic of
facility: Asan Medical Center
state: Seoul Teugbyeolsi
city: Georgetown
country: Malaysia
facility: Pulau Pinang Hospital
city: Kuala Lumpur
country: Malaysia
facility: University Malaya Medical Centre
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
city: Putrajaya
country: Malaysia
facility: National Cancer Institute (Institut Kanser Negara)
city: Chisinau
country: Moldova, Republic of
facility: The Institute of Oncology, Arensia Exploratory Medicine
city: Auckland
country: New Zealand
facility: Harbour Cancer and Wellness
city: Christchurch
country: New Zealand
facility: Nzcr Christchurch
city: Muang
country: Thailand
facility: Srinagarind Hospital (Khon Kaen University)
Study officials:
affiliation: BeiGene
name: Study Director
role: STUDY_DIRECTOR
References: