225Ac-TR2205 treatment for advanced triple-negative breast cancer

A Prospective, Open-label, Single-arm, Exploratory Clinical Trial to Evaluate the Safety and Tolerability of 225Ac-TR2205 Injection in Patients With Triple-negative Breast Cancer.

This trial will try 225Ac-TR2205, a targeted radioactive medicine, in adults with metastatic triple-negative breast cancer who have had at least two prior systemic treatments to see if it is safe, tolerable, and to gather early effectiveness and radiation dosimetry data.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Shandong Cancer Hospital and Institute (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT07340424 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-center, open-label, single-arm early-phase 1 trial testing 225Ac-TR2205 in patients with metastatic triple-negative breast cancer. The primary focus is on safety and tolerability, with secondary data collected on radiation dosimetry and initial anti-tumor activity using RECIST 1.1. Eligible participants are adult females with histologically confirmed TNBC, ECOG 0-1, at least one measurable lesion, and prior systemic therapy as specified. Treatments and follow-up imaging will be performed at the enrolling center to monitor toxicity and response.

Who should consider this trial

Good fit: Adult female patients (≥18 years) with histologically confirmed metastatic triple-negative breast cancer, ECOG 0-1, at least one measurable lesion by RECIST 1.1, and who have received at least two prior systemic treatments (including at least one for metastatic disease).

Not a fit: Patients with ECOG performance status >1, significant uncontrolled organ dysfunction or hematologic toxicity from prior treatments, those who do not meet the prior-therapy requirements, or those unable to receive a radiopharmaceutical are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could provide a new targeted radiopharmaceutical option for patients with heavily pretreated metastatic TNBC and help guide dosing with individualized dosimetry.

How similar studies have performed: Alpha-emitter radiopharmaceuticals have produced promising results in other cancer types, but 225Ac-TR2205 for TNBC is a novel, early-phase approach with limited prior clinical experience in this disease.

Eligibility criteria

Inclusion Criteria:

1. Voluntary participation in the study and signing of the informed consent form.
2. Female patients aged 18 years and above.
3. Patients with triple-negative breast cancer who have been diagnosed by histopathology \[immune histochemistry estrogen receptor (ER) positive rate \< 1% is defined as ER negative expression; progesterone receptor (PR) positive rate \< 1% is defined as PR negative; human epidermal growth factor receptor 2 (HER2) expression 0-1+ or HER2 ++ but fluorescence in situ hybridization/colorimetric in situ hybridization (FISH/CISH) negative is defined as HER2 negative expression\].
4. Patients with metastatic triple-negative breast cancer who have received at least 2 systemic treatments (at least 1 of which is for metastatic disease).
5. Patients with at least 1 measurable lesion (tumor evaluation according to RECIST 1.1).
6. ECOG performance status assessment of 0-1.
7. Clinical significance of hematological toxicity related to previous treatment must recover to ≤ 2 grade, and non-hematological toxicity ≤ 1 grade (except for hair loss).
8. For patients with reproductive potential: 7 days before the first administration, fertile women must confirm that the urine pregnancy test is negative and agree to use effective contraceptive measures during the use of the study drug and within 6 months after the last administration (such as oral contraceptives, intrauterine devices, restraint of sexual desire or barrier contraception combined with spermicides, etc.).

Exclusion Criteria:

1. Patients who received radiotherapy (except palliative radiotherapy) or chemotherapy, immunotherapy within 3 weeks before treatment, except for bisphosphonates (which can be used for bone metastasis), are excluded.
2. Patients who received radionuclide therapy within 6 months before enrollment, such as strontium-89, samarium-153, rhenium-186, rhenium-188, radium-223, lutetium-177, actinium-225, or whole-body radiotherapy.
3. Patients who are undergoing chemotherapy, immunotherapy, biological therapy, off-label radionuclide therapy, or other investigational treatments.
4. Patients who have undergone major surgery within 28 days before enrollment.
5. Patients evaluated by the investigator are expected to have a life expectancy of less than 3 months.
6. Bone scans show super bone imaging, defined as uniform and significant concentration of radioactive isotopes in the entire skeleton relative to soft tissue, while the urinary system is not visible or shows mild visibility.
7. Symptomatic spinal cord compression, or clinical or imaging evidence suggesting impending spinal cord compression.
8. Patients with uncontrollable central nervous system (CNS) metastases, who need symptomatic treatment with glucocorticoids or mannitol, and if necessary, enhanced CT or MRI to clarify the status of brain metastases.
9. Patients with a history of other malignant tumors, except for those with fully treated malignant tumors that have survived without treatment for more than 3 years without recurrence or progression, or patients with fully treated non-melanoma skin cancer and superficial bladder cancer.
10. Patients with a history that may interfere with the purpose of the study and assessment, or the investigator determines that the patient has any condition that cannot cooperate with imaging examinations, treatment, and procedures.

Where this trial is running

Jinan, Shandong

• Cancer Hospital of Shandong First Medical University — Jinan, Shandong, China (Recruiting)

Study contacts

• Study coordinator: Xiaorong Sun

Conditions Advanced Metastatic Triple-negative Breast Cancer