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

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.

NCT Number	NCT07137416
Lead Sponsor	National Cancer Institute (NCI)
Conditions	Anatomic Stage III Breast Cancer AJCC v8, Anatomic Stage IV Breast Cancer AJCC v8, Invasive Breast Carcinoma, Locally Advanced Breast Carcinoma, Metastatic Breast Carcinoma, Metastatic HER2-Low Breast Carcinoma, Metastatic HER2-Positive Breast Carcinoma, Metastatic Hormone Receptor-Positive Breast Carcinoma +8 more
Enrollment	36 participants
Start Date	2026-10-05
Primary Completion	2028-01-10 (estimated)
Study Completion	2028-01-10 (estimated)
Updated on ClinicalTrials.gov	2026-07-13