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

Cancer Categories

Brain and Nervous System,Breast,Gastrointestinal (GI),Genitourinary (GU),Gynecologic,Head and Neck,Lung,Skin

Karmanos Trial ID

NCT ID

Age Group

Scope

Phase

Principal Investigator

Phase 1a Dose Escalation

Primary Objectives:

To assess the safety and tolerability of BGB-43395 alone in patients with advanced solid tumors or as part of combination therapies in HR+/HER2- breast cancer and other selected tumor types.
To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) and recommended dose(s) for expansion (RDFE[s]) of BGB-43395 alone in patients with advanced solid tumors or as part of combination therapies in HR+/HER2- breast cancer and other selected tumor types.

Secondary Objectives:

To assess the preliminary anticancer activity of BGB-43395 alone in patients with advanced solid tumors or as part of combination therapies in HR+/HER2- breast cancer and other selected tumor types.
To characterize the PK of BGB-43395 and its metabolite, BGB-48579, alone in patients with advanced solid tumors or as part of combination therapies in HR+/HER2- breast cancer and other selected tumor types.

Phase 1b: Dose Expansion Objectives and Endpoints

Primary Objectives:

To assess the antitumor activity in patients treated with BGB-43395 alone or as part of combination therapies in selected tumor cohorts.

Secondary Objectives:

To further assess the antitumor activity in patients treated with BGB-43395 alone or as part of combination therapies in selected tumor cohorts.
To further characterize the safety and tolerability of BGB-43395 alone or as part of combination therapies.
To further characterize the pharmacokinetics (PK) of BGB-43395 and its metabolite, BGB-48579, with combination therapies.

Eligibility

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.
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.
History of hepatitis B or active hepatitis C infection.
Prior allogeneic stem cell transplantation, or organ transplantation.

Locations

4100 John R
Detroit, MI 48201
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Phone: 1-800-527-6266

31995 Northwestern Hwy
Farmington Hills, MI 48334
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Phone: 1-800-527-6266

Applicable Disease Site

Therapies, Drugs, Devices