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

Non-small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06120283
• Other study ID #: BGB-43395-101
• Secondary ID: 2023-506888-34-0
• Status: Recruiting
• Phase: Phase 1
• Start date: December 1, 2023
• Est. completion date: May 2026

Study information

• Verified date: April 2024
• Source: BeiGene
• Contact: Study Director
• Phone: 1.877.828.5568
• Email: clinicaltrials[@]beigene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 79
• Est. completion date: May 2026
• Est. primary completion date: May 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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, 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.
• Phase 1b (Dose Expansion): 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.
• 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 metastasis.
• Any malignancy = 3 years before the first dose of study drug(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.

Related Conditions & MeSH terms

• Advanced Breast Cancer
• Advanced Solid Tumor
• Breast Neoplasms
• Carcinoma, Non-Small-Cell Lung
• HER2-negative Breast Cancer
• Hormone Receptor Positive Breast Carcinoma
• Hormone Receptor Positive HER-2 Negative Breast Cancer
• Hormone Receptor Positive Malignant Neoplasm of Breast
• Metastatic Breast Cancer
• Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• BGB-43395
Planned doses administered orally.
• Fulvestrant
Standard dose administered via intramuscular injection.
• Letrozole
Standard dose administered orally as a tablet.

Locations

Country	Name	City	State
Australia	Blacktown Cancer and Haematology Centre	Blacktown	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Peter Maccallum Cancer Centre	Melbourne	Victoria
Australia	Macquarie University	North Ryde	New South Wales
United States	James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	Sarah Cannon Research Institute (Scri) At Health One	Denver	Colorado
United States	Duke Cancer Center	Durham	North Carolina
United States	The University of Texas Md Anderson Cancer Center	Houston	Texas
United States	Next Oncology	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 criteria.	Up to approximately 3 years
Primary	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 3 years
Primary	Phase 1a: Recommended Dose for Expansion (RDFE) of BGB-43395	RDFE of BGB-43395 alone or in combination with fulvestrant or letrozole will be determined based upon the MTD or MAD.	Up to approximately 3 years
Primary	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 3 years
Secondary	Phase 1a: ORR	ORR is defined as the percentage of participants who have confirmed CR or PR assessed by the investigator using RECIST v1.1.	Up to approximately 3 years
Secondary	Phase 1a and 1b: Duration of Response (DOR)	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.	Up to approximately 3 years
Secondary	Phase 1a and 1b: Time to Response (TTR)	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.	Up to approximately 3 years
Secondary	Phase 1b: Disease Control Rate (DCR)	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.	Up to approximately 3 years
Secondary	Phase 1b: Clinical Benefit Rate (CBR)	CBR is defined as the percentage of participants with best overall response of confirmed CR, PR, or stable disease lasting = 24 weeks.	Up to approximately 3 years
Secondary	Phase 1b: Progression-Free Survival (PFS)	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.	Up to approximately 3 years
Secondary	Phase 1b: 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), and laboratory assessments.	Up to approximately 3 years
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)