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 study is testing a new combination of two cancer drugs — CX-5461 (pidnarulex) and trastuzumab deruxtecan (T-DXd) — in people with HER2-positive solid tumors, with a focus on breast cancer. HER2-positive means the cancer cells have a protein on their surface that makes them grow faster. The study first tests safety at increasing doses, then expands to a larger group of breast cancer patients. **You may be eligible if...** - You are 18 years or older - You have HER2-positive advanced or metastatic breast cancer (or another solid tumor that has not responded to standard treatments, in the dose-finding phase) - Your general health and organ function meet specific laboratory thresholds - You are willing to provide a tumor tissue sample **You may NOT be eligible if...** - You are under 18 years old - You have significant heart, liver, or kidney problems - You have active or uncontrolled brain metastases - You have a history of certain lung conditions (interstitial lung disease or pneumonitis) - You are pregnant or breastfeeding Talk to your doctor to see if this trial is right for you.