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RecruitingNCT07137416

Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer

Phase 1b Study of Pidnarulex and Trastuzumab Deruxtecan in Patients With HER2 Expressing Solid Tumors

Status
Recruiting
Phase
Phase 1
Study type
Interventional
Enrollment
36 (estimated)
Sponsor
National Cancer Institute (NCI) · NIH
Sex
All
Age
18 Years
Healthy volunteers
Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of pidnarulex in combination with trastuzumab deruxtecan in treating patients with breast cancer and other solid tumors that express varying levels of a protein called HER2 and that has spread from where it first started (primary site) to other places in the body (metastatic), that cannot be removed by surgery (unresectable), or that has spread to nearby tissue or lymph nodes (locally advanced). Pidnarulex is an enzyme inhibitor that causes cell death and prevents tumor cell growth. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive tumor cells in a targeted way and delivers deruxtecan to kill them. Giving pidnarulex in combination with trastuzumab deruxtecan may be safe, tolerable and/or effective in treating patients with metastatic, unresectable, or locally advanced HER2-expressing breast cancer or other solid tumors.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of CX-5461 (pidnarulex) when used in combination with trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer, hormone receptor (HR)-positive HER2-ultralow breast cancer or HER2-positive (immunohistochemistry \[IHC\] 3+) solid tumors. (Dose escalation primary objective) II. To evaluate safety and tolerability of the combination of CX-5461 (pidnarulex) with T-DXd at the RP2D in patients with HER2-low breast cancer and HR-positive HER2-ultralow breast cancer. (Dose expansion primary objective) SECONDARY OBJECTIVES: I. To observe and record anti-tumor activity. II. To evaluate the plasma pharmacokinetic (PK) profiles of CX-5461 (pidnarulex) and T-DXd when administered in combination. III. To determine markers of deoxyribonucleic acid (DNA) damage response (DDR) in tumor specimens at baseline and on-treatment in patients with HER2-low and ultralow breast cancer in the dose expansion cohort (pharmacodynamic \[PD\] objective). OUTLINE: This is a dose-escalation study of pidnarulex followed by a dose-expansion study. Patients receive pidnarulex intravenously (IV) over 60 minutes on day 8 of each cycle and T-DXd IV over 30-90 minutes on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA), collection of blood samples, and radiologic imaging throughout the trial. Patients may also undergo biopsy throughout the trial. After completion of study treatment, patients are followed up at 30 days and then for 3 years.

Conditions

Interventions

TypeNameDescription
PROCEDUREBiopsy ProcedureUndergo biopsy
PROCEDUREBiospecimen CollectionUndergo collection of blood samples
PROCEDUREEchocardiography TestUndergo ECHO
PROCEDUREMultigated Acquisition ScanUndergo MUGA
DRUGPidnarulexGiven IV
PROCEDURERadiologic Imaging ProcedureUndergo radiologic imaging
BIOLOGICALTrastuzumab DeruxtecanGiven IV

Timeline

Start date
2026-10-05
Primary completion
2028-01-10
Completion
2028-01-10
First posted
2025-08-22
Last updated
2026-04-13

Locations

1 site across 1 country: United States

Regulatory

Source: ClinicalTrials.gov record NCT07137416. Inclusion in this directory is not an endorsement.