BGB-43395 Alone or as Part of Combination Therapies in Chinese Participants With HR+/HER2- Breast Cancer and Other Advanced Solid Tumors

NCT06253195 | Active Not Recruiting Phase 1 DMC

• 2 other identifiers: BGB-43395-102CTR20240674
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 7

Brief Summary

This is an open-label, multicenter, phase 1a/1b clinical study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGB-43395, a cyclin-dependent kinase 4 (CDK4) inhibitor, as monotherapy or in combination with fulvestrant, letrozole, or other combination partners in Chinese participants with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-) breast cancer (BC) and other advanced or metastatic solid tumors.

Conditions

Advanced Solid Tumor; Metastatic Solid Tumor; Hormone-receptor-positive Breast Cancer; Breast Cancer; Metastatic Breast Cancer; Hormone Receptor Positive Malignant Neoplasm of Breast; HER2-negative Breast Cancer

Keywords

advanced solid tumor; metastatic solid tumor; BGB-43395; breast cancer; HR+/HER2- breast cancer; hormone receptor positive breast 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), and laboratory assessments as needed, and that meet protocol-defined dose-limiting toxicity (DLT) criteria.

  Up to approximately 30 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. MAD is defined as the highest dose administered if MTD is not reached.

  Up to approximately 30 months

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

  RDFE of BGB-43395 alone or as part of combination therapies will be determined based upon the MTD or MAD.

  Up to approximately 30 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) as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  Up to approximately 30 months

Secondary Outcomes (12)

• Phase 1a: ORR

  Up to approximately 30 months

• Phase 1b: Progression-Free Survival (PFS)

  Up to approximately 30 months

• Phase 1b: Number of Participants with AEs and SAEs

  Up to approximately 30 months

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

  Up to approximately 30 months

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

  Up to approximately 30 months

Study Arms (2)

Phase 1a: Dose Escalation

EXPERIMENTAL

Sequential cohorts of increasing dose levels of BGB-43395 will be evaluated as monotherapy and in combination with either fulvestrant or letrozole.

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

Phase 1b: Dose Expansion

EXPERIMENTAL

The recommended dose for expansion (RDFE) for BGB-43395 in combination with fulvestrant from Phase 1a will be evaluated in HR+ breast cancer and selected tumor cohorts.

Drug: BGB-43395; Drug: Fulvestrant

Interventions

BGB-43395 DRUG

Administered orally.

Phase 1a: Dose Escalation; Phase 1b: Dose Expansion

Fulvestrant DRUG

Administered via intramuscular injection.

Phase 1a: Dose Escalation; Phase 1b: Dose Expansion

Letrozole DRUG

Administered orally.

Phase 1a: 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 locally advanced or metastatic solid tumors associated with CDK4 dependency, including HR+/HER2- breast cancer. Participants must have received prior standard-of-care therapies for their disease, unless the therapy is not available or not tolerated, or is determined not appropriate based on the investigator's judgment.
• Phase 1b (Dose Expansion): Participants with selected solid tumors including locally advanced or metastatic HR+/HER2- breast cancer.
• Female participants with metastatic HR+/HER2- breast cancer will be required to have ovarian function suppression using gonadotropin-releasing hormone (GnRH) agonists such as goserelin or be postmenopausal.
• Male participants with HR+/HER2- breast cancer will be required to have gonadal suppression using GnRH agonists when being treated with letrozole or fulvestrant.
• Patients must have ≥1 measurable lesion per RECIST v1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
• Adequate organ function without symptomatic visceral disease.

You may not qualify if:

• Prior therapy selectively targeting CDK4 (prior CDK4/6 inhibitor therapy is permitted).
• 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. Patients receiving prophylactic antibiotics (eg, for prevention of urinary tract infection, chronic obstructive pulmonary disease, or for dental extraction) are eligible. Patients who have recovered from symptomatic COVID-19 infection can be rescreened for this study.
• Untreated chronic hepatitis B or active hepatitis C infection.

Sponsors & Collaborators

• BeiGene: lead

Study Sites (7)

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

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

Guangzhou, Guangdong, 510245, China

Location

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, 530021, China

Location

The First Affiliated Hospital of Nanchang University Branch Donghu

Nanchang, Jiangxi, 330006, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Breast Neoplasms

Interventions

Fulvestrant; Letrozole

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue 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

  BeiGene

  STUDY DIRECTOR

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: February 2, 2024
• First Posted: February 12, 2024
• Study Start: April 1, 2024
• Primary Completion: February 28, 2026
• Study Completion (Estimated): October 26, 2026
• Last Updated: June 5, 2025

Record last verified: 2025-06

Data Sharing

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

Locations

CN (7)