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

NCT06120283 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: BGB-43395-1012023-506888-34-00CTR20243370
• Study Type: interventional
• Target: 399
• Locations: 11 countries
• Sites: 63

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.

Conditions

Advanced Solid Tumor; Hormone Receptor Positive Breast Carcinoma; Metastatic Breast Cancer; HER2-negative Breast Cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer; Non-small Cell Lung Cancer; Advanced Breast Cancer; Hormone-receptor-positive Breast Cancer; Hormone Receptor Positive Malignant Neoplasm of Breast

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

Outcome Measures

Primary Outcomes (4)

• Phase 1a: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  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.

  Up to approximately 60 months

• Phase 1a: Maximum Tolerated Dose (MTD) or Maximum Administered Dose (MAD) of BGB-43395

  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.

  Up to approximately 60 months

• Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395

  RDFE of BGB-43395 alone or in combination with fulvestrant, letrozole, or elacestrant will be determined based upon the MTD or MAD.

  Up to approximately 60 months

• Phase 1b: Objective Response Rate (ORR)

  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.

  Up to approximately 60 months

Secondary Outcomes (12)

• Phase 1a: ORR

  Up to approximately 60 months

• Phase 1a and 1b: Duration of Response (DOR)

  Up to approximately 60 months

• Phase 1a and 1b: Time to Response (TTR)

  Up to approximately 60 months

• Phase 1b: Disease Control Rate (DCR)

  Up to approximately 60 months

• Phase 1b: Clinical Benefit Rate (CBR)

  Up to approximately 60 months

Study Arms (5)

Dose Escalation

EXPERIMENTAL

Phase 1a: Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant, letrozole, or elacestrant to assess for safety and tolerability.

Drug: BGB-43395; Drug: Fulvestrant; Drug: Letrozole; Drug: Elacestrant

Safety Expansion

EXPERIMENTAL

Phase 1a: Cohorts of selected dose levels of BGB-43395 in combination with fulvestrant or letrozole in HR+/HER2 breast cancer.

Drug: BGB-43395; Drug: Fulvestrant; Drug: Letrozole

Dose Expansion Cohort 1

EXPERIMENTAL

Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 (in combination with fulvestrant) from Phase 1a will be evaluated in HR+ breast cancer.

Drug: BGB-43395; Drug: Fulvestrant

Dose Expansion Cohort 2

EXPERIMENTAL

Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 in combination with letrozole from Phase 1a will be evaluated in HR+ breast cancer.

Drug: BGB-43395; Drug: Letrozole

Dose Expansion Cohort 3

EXPERIMENTAL

Phase 1b: The recommended dose for expansion (RFDE) for BGB-43395 in combination with letrozole from Phase 1a will be evaluated in HR+ breast cancer. Participants will also receive an anti-diarrheal agent for prophylaxis.

Drug: BGB-43395; Drug: Letrozole; Drug: Anti-Diarrheal Agent

Interventions

BGB-43395 DRUG

Planned doses administered orally.

Dose Escalation; Dose Expansion Cohort 1; Dose Expansion Cohort 2; Dose Expansion Cohort 3; Safety Expansion

Fulvestrant DRUG

Standard dose administered via intramuscular injection.

Dose Escalation; Dose Expansion Cohort 1; Safety Expansion

Letrozole DRUG

Standard dose administered orally as a tablet.

Dose Escalation; Dose Expansion Cohort 2; Dose Expansion Cohort 3; Safety Expansion

Anti-Diarrheal Agent DRUG

Administered orally as a tablet.

Dose Expansion Cohort 3

Elacestrant DRUG

Standard dose administered orally as a tablet.

Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• BeOne Medicines: lead

Study Sites (63)

Sarah Cannon Research Institute (Scri) At Health One

Denver, Colorado, 80218-1238, United States

RECRUITING

Florida Cancer Specialists and Research Institute

Lake Mary, Florida, 32746-2115, United States

COMPLETED

Karmanos Cancer Institute

Detroit, Michigan, 48201-2013, United States

COMPLETED

Washington University School of Medicine

St Louis, Missouri, 63110-1010, United States

RECRUITING

Duke Cancer Center

Durham, North Carolina, 27710-2000, United States

RECRUITING

James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210-1240, United States

RECRUITING

Scri Oncology Partners

Nashville, Tennessee, 37203-1503, United States

RECRUITING

The University of Texas Md Anderson Cancer Center

Houston, Texas, 77030-4009, United States

RECRUITING

Next Dallas

Irving, Texas, 75039-2743, United States

RECRUITING

Next Oncology

San Antonio, Texas, 78229-6028, United States

RECRUITING

Blacktown Cancer and Haematology Centre

Blacktown, New South Wales, NSW 2148, Australia

RECRUITING

Southern Highlands Private Hospital

Bowral, New South Wales, NSW 2576, Australia

RECRUITING

Concord Repatriation General Hospital

Concord, New South Wales, NSW 2139, Australia

RECRUITING

Macquarie University

North Ryde, New South Wales, NSW 2109, Australia

RECRUITING

Townsville University Hospital

Douglas, Queensland, QLD 4814, Australia

RECRUITING

Genesiscare St Andrews

Adelaide, South Australia, SA 5000, Australia

RECRUITING

Austin Health

Heidelberg, Victoria, VIC 3084, Australia

ACTIVE NOT RECRUITING

Peter Maccallum Cancer Centre

Melbourne, Victoria, VIC 3000, Australia

RECRUITING

Fundacao Pio Xii Hospital de Amor de Barretos

Barretos, 14.784-400, Brazil

RECRUITING

Hospital Sirio Libanes Brasilia

Brasília, 70200-730, Brazil

RECRUITING

Centro de Pesquisas Oncologicas Cepon

Florianópolis, 88034-000, Brazil

RECRUITING

Liga Norte Riograndene Contra O Cancer

Natal, 59062-000, Brazil

RECRUITING

Fundacao Universidade de Caxias Do Sul Instituto de Pesquisas Em Saude

Petrópolis, 95070-560, Brazil

RECRUITING

Hospital Sao Lucas Da Pucrs Uniao Brasileira de Educacao E Assistencia

Porto Algre, 90610-000, Brazil

RECRUITING

Instituto Nacional de Cancer

Rio de Janeiro, 20560-120, Brazil

RECRUITING

Instituto Dor de Pesquisa E Ensino Hospital Sao Rafael

Salvador, 41253-190, Brazil

RECRUITING

Icesp Instituto Do Cancer Do Estado de Sao Paulo Octavio Frias de Oliveira

São Paulo, 01246-000, Brazil

RECRUITING

Clinica de Pesquisa E Centro de Estudos Em Oncologia Ginecologica E Mamaria

São Paulo, 01318-001, Brazil

RECRUITING

Hospital Israelita Albert Einstein

São Paulo, 05652-900, Brazil

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

RECRUITING

Sun Yat Sen Memorial Hospital, Sun Yat Sen University (South)

Guangzhou, Guangdong, 510245, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

RECRUITING

The First Affiliated Hospital of Nanchang University Branch Donghu

Nanchang, Jiangxi, 330006, China

RECRUITING

Liaoning Cancer Hospital and Institute

Shenyang, Liaoning, 110042, China

RECRUITING

Fudan University Shanghai Cancer Centerpudong

Shanghai, Shanghai Municipality, 201321, China

RECRUITING

Centre de Lutte Contre Le Cancer Institut Bergonie

Bordeaux, 33000, France

RECRUITING

Centre Francois Baclesse

Caen, 14000, France

RECRUITING

Centre Oscar Lambret

Lille, 59000, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13009, France

RECRUITING

Institut Curie

Paris, 75005, France

RECRUITING

Centre Eugene Marquis

Rennes, 35043, France

RECRUITING

Institut de Cancerologie de Louest

Saint-Herblain, 44800, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94800, France

RECRUITING

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

RECRUITING

Shizuoka Cancer Center

Suntogun, Shizuoka, 411-8777, Japan

RECRUITING

Pulau Pinang Hospital

George Town, 10450, Malaysia

RECRUITING

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

RECRUITING

Sarawak General Hospital

Kuching, 93586, Malaysia

RECRUITING

National Cancer Institute (Institut Kanser Negara)

Putrajaya, 62250, Malaysia

RECRUITING

The Institute of Oncology, Arensia Exploratory Medicine

Chisinau, 2025, Moldova

RECRUITING

Harbour Cancer and Wellness

Auckland, 1023, New Zealand

RECRUITING

Nzcr Christchurch

Christchurch, 8011, New Zealand

RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

RECRUITING

Gachon University Gil Medical Center

NamdongGu, Incheon Gwang'yeogsi, 21565, South Korea

RECRUITING

Samsung Medical Center

GangnamGu, Seoul Teugbyeolsi, 06351, South Korea

RECRUITING

The Catholic University of Korea, Seoul St Marys Hospital

SeochoGu, Seoul Teugbyeolsi, 06591, South Korea

RECRUITING

Severance Hospital Yonsei University Health System

SeodaemunGu, Seoul Teugbyeolsi, 03722, South Korea

RECRUITING

Korea University Anam Hospital

SeongbukGu, Seoul Teugbyeolsi, 02841, South Korea

RECRUITING

Seoul National University Hospital

Seoul, Seoul Teugbyeolsi, 03080, South Korea

RECRUITING

Asan Medical Center

SongpaGu, Seoul Teugbyeolsi, 05505, South Korea

RECRUITING

Srinagarind Hospital (Khon Kaen University)

Muang, 40002, Thailand

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

Fulvestrant; Letrozole; elacestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Study Director

  BeOne Medicines

  STUDY DIRECTOR

Central Study Contacts

Study Director

CONTACT

1.877.828.5568; clinicaltrials@beonemed.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 2023
• First Posted: November 7, 2023
• Study Start: December 1, 2023
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: July 23, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: See plan description
• Access Criteria: See plan description

Locations

MY (4); JP (3); NZ (2); TH (1); MO (1); US (10); AU (8); FR (8); CN (7); KR (8); BR (11)