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

BeiGene

Status and phase: Enrolling; Phase 1

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT06253195

CTR20240674 (Registry Identifier)

BGB-43395-102

Details and patient eligibility

About

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.

Enrollment: 78 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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.

Exclusion criteria

• 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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78 participants in 2 patient groups

Phase 1a: Dose Escalation

Experimental group

Description:

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

Treatment:

Drug: BGB-43395

Drug: Fulvestrant

Drug: Letrozole

Phase 1b: Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: BGB-43395

Drug: Fulvestrant