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

Phase 1

Recruiting

• Conditions: Advanced Solid Tumor; Hormone Receptor Positive Malignant Neoplasm of Breast; Advanced Breast Cancer; Metastatic Breast Cancer; Hormone-receptor-positive Breast Cancer; HER2-negative Breast Cancer; Hormone Receptor Positive HER-2 Negative Breast Cancer; Non-small Cell Lung Cancer; Hormone Receptor Positive Breast Carcinoma
• Interventions: Drug: BGB-43395; Drug: Fulvestrant; Drug: Letrozole; Drug: Elacestrant

• Registration Number: NCT06120283
• Lead Sponsor: BeiGene

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-11-01
• Study First Submitted QC: 2023-11-01
• Study First Posted: 2023-11-07
• Study Start: 2023-12-01
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-13
• Last Update Posted: 2025-06-17
• Primary Completion: 2028-06
• Study Completion: 2028-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Dose Escalation and Safety Expansion	BGB-43395	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.
Dose Escalation and Safety Expansion	Fulvestrant	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.
Dose Escalation and Safety Expansion	Letrozole	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.
Dose Escalation and Safety Expansion	Elacestrant	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.
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.
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.

Primary Outcome Measures

Name	Time	Method
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: Recommended Dose for Expansion (RDFE) of BGB-43395	Up to approximately 60 months	RDFE of BGB-43395 alone or in combination with fulvestrant, letrozole, or elacestrant will be determined based upon the MTD or MAD.
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: 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.

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 (63)

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

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