Phase 1b Study of Pidnarulex and Trastuzumab Deruxtecan in Patients With HER2 Expressing Solid Tumors
National Cancer Institute (NCI)
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.
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 HER…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * DOSE ESCALATION PHASE ONLY: Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective * DOSE EXPANSION PHASE ONLY: Participants must have histologically or cytologically confirmed invasive breast cancer, with either locally advanced or metastatic disease * Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of CX-5461 (pidnarulex) in combination with T-DXd in patients \< 18 years of age, children are exclude…
Interventions
- ProcedureBiopsy Procedure
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- ProcedureEchocardiography Test
Undergo ECHO
- ProcedureMultigated Acquisition Scan
Undergo MUGA
- DrugPidnarulex
Given IV
- ProcedureRadiologic Imaging Procedure
Undergo radiologic imaging
- BiologicalTrastuzumab Deruxtecan
Location
- Dana-Farber - Harvard Cancer Center LAOBoston, Massachusetts