PD-L1 Inhibitor + RT ± Ursodeoxycholic Acid in Recurrent/Metastatic HER2-Neg Breast Cancer

Last updated: February 19, 2025
Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Overall Status: Active - Not Recruiting

Phase

2

Condition

Breast Cancer

Cancer

Treatment

Ursodeoxycholic Acid (URSO)

Radiotherapy

Adebrelimab (PD-L1 inhibitor)

Clinical Study ID

NCT06842472
NCC5137；Approve No.25/004-0004
  • Ages > 18
  • Female

Study Summary

Experimental Group Adebrelimab (PD-L1 inhibitor) 1200 mg on Day 1, every 3 weeks. Radiotherapy (Stereotactic Body Radiation Therapy, SBRT) with a dose of 24 Gy/3 fractions within 3 weeks after the first immunotherapy dose.

Ursodeoxycholic Acid (UDCA) 250 mg twice daily, starting 7 days before radiotherapy and continuing for 1 month after radiotherapy completion.

Control Group Adebrelimab 1200 mg on Day 1, every 3 weeks. SBRT with a dose of 24 Gy/3 fractions within 3 weeks after the first immunotherapy dose.

Chemotherapy is permitted during the study in both groups. The decision to use chemotherapy will be made by the treating physician based on the patient's individual condition and prior treatment history.

Primary Endpoint Objective Response Rate (ORR) of lesions outside the radiotherapy field, assessed by RECIST 1.1 criteria.

Secondary Endpoints Disease Control Rate (DCR) of lesions outside the radiotherapy field. Safety profile (≥3 toxicities). ORR of lesions within the radiotherapy field. Distant metastasis rate outside the radiotherapy field. Progression-Free Survival (PFS) and Overall Survival (OS).

Safety Monitoring Adverse events and serious adverse events (SAE) will be closely monitored and reported according to the protocol. Treatment will be discontinued if predefined criteria for stopping are met.

Study Duration The study will include a screening period, a treatment period, and a follow-up period with regular assessments every 2 cycles of immunotherapy until death occurs.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Age ≥ 18 years；

  2. Patients with recurrent/metastatic HER2-negative breast cancer；

  3. Patients who have previously received standard treatment regimens forrecurrent/metastatic breast cancer；

  4. At least one lesion suitable for radiation therapy；

  5. At least one measurable metastatic lesion outside of the radiation field, and can bemonitored using the "Response Evaluation Criteria in Solid Tumors" (RECIST) version 1.1；

  6. ECOG performance status of 0-2；

  7. Signed informed consent；

  8. Patients who have previously received radiation therapy may be included as long asit does not interfere with irradiation of the target lesion；

Exclusion

Exclusion Criteria:

  1. Biliary obstruction, acute or chronic cholecystitis or cholangitis, or long-termbiliary colic (contraindication for UDCA)；

  2. Malabsorption syndrome or diseases that significantly affect gastrointestinalfunction; patients who have undergone total gastrectomy or resection of the proximalsmall intestine that may affect oral drug absorption；

  3. Exclusion of patients with symptomatic brain metastases or leptomeningealmetastasis; patients with brain metastases who have been treated and stabilized (with no progression within 4 weeks) may be included, but brain metastases cannot beused as target lesions；

  4. Known invasive malignancies within the past 5 years that are still progressing orrequire active treatment (excluding patients with basal cell carcinoma, squamouscell carcinoma of the skin, or breast ductal carcinoma in situ or cervical carcinomain situ who have received curative treatment)；

  5. Previous immune therapy resulting in grade 3 or higher adverse events； Diagnosedwith immunodeficiency or receiving long-term systemic corticosteroid treatment (prednisone equivalent dose >10 mg daily) or any form of immunosuppressive therapywithin 7 days before the first dose of study treatment；

  6. Active autoimmune diseases requiring systemic treatment (e.g., usingdisease-modifying drugs, corticosteroids, or immunosuppressive drugs) within thepast 2 years；

  7. Active infections requiring systemic treatment；

  8. Known history of active tuberculosis；

  9. Other significant cardiovascular diseases, including recent myocardial infarction,acute coronary syndrome, or a history of coronary artery interventions (angioplasty,stent placement, or bypass surgery) within the last 6 months; NYHA Class II-IVcongestive heart failure (CHF) or a history of NYHA Class III or IV CHF；

  10. Known history of human immunodeficiency virus (HIV) infection

Study Design

Total Participants: 70
Treatment Group(s): 3
Primary Treatment: Ursodeoxycholic Acid (URSO)
Phase: 2
Study Start date:
February 01, 2025
Estimated Completion Date:
December 31, 2029