NCT06590558

Testing the Addition of an Investigational Anti-Cancer Drug, ASTX660 (Tolinapant), to a Usual Chemotherapy Treatment (Eribulin) for Treatment of Advanced Triple Negative Breast Cancer

Phase I/Ib Study of Eribulin in Combination With ASTX660 (Tolinapant) in Metastatic Triple Negative Breast Cancer (TNBC)

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I/Ib trial tests the safety, side effects, best dose, and effectiveness of ASTX660 (tolinapant) in combination with eribulin mesylate (eribulin) in treating patients with triple negative breast cancer that cannot be removed by surgery (unresectable) or that has spread to nearby tissues or lymph nodes (locally advanced) or to other places in the body (metastatic). Tolinapant may stop the growth of tumor cells by blocking proteins, such as XIAP and cIAP1, needed for tumor cell survival. Chemotherapy drugs, such as eribulin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving tolinapant in combination with eribulin may be safe, tolerable, and/or effective in treating patients with unresectable, locally advanced, or metastatic triple negative breast cancer.

Detailed description

PRIMARY OBJECTIVES: I. Determine the safety and tolerability of ASTX660 (tolinapant) in combination with eribulin in patients with metastatic breast cancer. II. Determine the maximum tolerated dose (MTD) of ASTX660 (tolinapant) in combination with eribulin. SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. Determine the pharmacokinetic parameters of ASTX660 (tolinapant) and eribulin when used in combination. III. Determine the pharmacodynamic parameters of antitumor activity of ASTX660 (tolinapant) and eribulin combination. EXPLORATORY OBJECTIVES: I. Develop biomarkers predictive of response and resistance to ASTX660 (tolinapant) in combination with eribulin in metastatic triple negative breast cancer. II. Investigate biomarkers and mechanisms of primary and secondary resistance to ASTX660 (tolinapant) in combination with eribulin in metastatic triple negative breast cancer. OUTLINE: This is a dose-escalation study of tolinapant in combination with eribulin followed by a dose-expansion study. Patients receive tolinapant orally (PO) once daily (QD) on days 1-7 and 15-21 and eribulin intravenously (IV) over 2-5 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, tissue biopsy, chest X-ray, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. After completion of study treatment, patients are followed for up to 3 months.

Conditions

• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Invasive Breast Carcinoma
• Locally Advanced HER2-Negative Breast Carcinoma
• Locally Advanced Hormone Receptor-Positive Breast Carcinoma
• Locally Advanced Triple-Negative Breast Carcinoma
• Metastatic HER2-Negative Breast Carcinoma
• Metastatic Hormone Receptor-Positive Breast Carcinoma
• Metastatic Triple-Negative Breast Carcinoma
• Unresectable HER2-Negative Breast Carcinoma
• Unresectable Hormone Receptor-Positive Breast Carcinoma
• Unresectable Triple-Negative Breast Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy Procedure	Undergo tissue biopsy
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Eribulin Mesylate	Given IV
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
DRUG	Tolinapant	Given PO
PROCEDURE	X-Ray Imaging	Undergo chest X-ray

Timeline

• Start date: 2025-08-04
• Primary completion: 2027-05-17
• Completion: 2027-05-17
• First posted: 2024-09-19
• Last updated: 2025-07-03

Regulatory

• FDA-regulated drug study