Actively Recruiting
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
Led by National Cancer Institute (NCI) · Updated on 2026-05-13
36
Participants Needed
1
Research Sites
66 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
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.
CONDITIONS
Official Title
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
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Patients with histologically confirmed metastatic or unresectable malignancy without effective standard treatments (dose escalation phase only)
- Patients with invasive breast cancer that is locally advanced or metastatic (dose expansion phase only)
- Age 18 years or older
- ECOG performance status 0 to 2 (Karnofsky score 60% or higher)
- Absolute neutrophil count 1,500/mcL or higher
- No granulocyte colony-stimulating factor use within 1 week before screening
- Platelet count 100,000/mcL or higher
- No red blood cell or platelet transfusions within 1 week before screening
- Total bilirubin 1.5 times or less the institutional upper limit of normal (ULN), or 2 times ULN for Gilbert's syndrome
- AST and ALT 3 times or less ULN (or 5 times ULN if liver metastases present)
- INR/PT and aPTT 1.5 times or less ULN
- Glomerular filtration rate 60 mL/min/1.73 m2 or higher
- At least one prior cytotoxic chemotherapy line; no progression on prior anthracycline in metastatic setting
- Prior PARP inhibitor treatment allowed
- HER2-positive solid cancers or HER2-low/ultralow breast cancer or triple negative breast cancer (dose escalation phase only)
- HER2-low or hormone receptor-positive HER2-ultralow breast cancer with measurable lesion outside prior radiation field (dose expansion phase only)
- Peripheral neuropathy grade 1 or less
- Left ventricular ejection fraction 50% or higher within 28 days before enrollment
- HIV patients on effective therapy with undetectable viral load within 6 months
- Controlled hepatitis B or cured hepatitis C infection
- Treated brain metastases without progression
- Patients with active brain metastases if no immediate CNS treatment is needed
- Cardiac function class II or better by NYHA classification
- Prior or concurrent malignancies not interfering with study
- Use of adequate contraception for women of childbearing potential and men during and after study
- Women of non-childbearing potential defined by surgical or menopausal status
- Male patients must not freeze or donate sperm during and 6 months after study
- Female patients must not donate or retrieve ova during and 7 months after study
- Ability to understand and sign informed consent
- No chest radiation therapy within 4 weeks (2 weeks for palliative stereotactic radiation)
You will not qualify if you...
- History of interstitial lung disease requiring steroids, current ILD, or suspected ILD not ruled out by imaging
- Severe pulmonary illnesses including recent pulmonary emboli, severe asthma, COPD, restrictive lung disease, pleural effusion, or autoimmune conditions with lung involvement
- Chemotherapy within 3 weeks (or longer for some agents)
- Cancer immunotherapy within 4 weeks
- Major surgery within 4 weeks
- Unresolved toxicities from previous anticancer therapy above grade 1 except alopecia
- Use of strong CYP3A4 inhibitors or inducers
- Use of other investigational agents
- History of severe allergic reactions to study drugs or similar compounds
- Corrected QT interval prolongation beyond specified limits
- Significant corneal or ocular surface disease
- Uncontrolled intercurrent illness or conditions making participation hazardous
- Pregnant or breastfeeding women due to potential risks of study drugs
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Dana-Farber - Harvard Cancer Center LAO
Boston, Massachusetts, United States, 02115
Actively Recruiting
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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