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

A Prospective Phase II Randomized Clinical Trial of PD-L1 Monoclonal Antibody in Combination with Radiation Therapy, with or Without Ursodeoxycholic Acid, in Patients with Recurrent or Metastatic HER2-Negative Breast Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Ursodeoxycholic Acid (URSO); Radiation: Radiotherapy; Drug: Adebrelimab (PD-L1 inhibitor)

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Min Deng, Doctor; Phone Number: 13661135602; Email: 923791362@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 18 years；
2. Patients with recurrent/metastatic HER2-negative breast cancer；
3. Patients who have previously received standard treatment regimens for recurrent/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 be monitored 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 as it does not interfere with irradiation of the target lesion；

Exclusion Criteria:

1. Biliary obstruction, acute or chronic cholecystitis or cholangitis, or long-term biliary colic (contraindication for UDCA)；
2. Malabsorption syndrome or diseases that significantly affect gastrointestinal function; patients who have undergone total gastrectomy or resection of the proximal small intestine that may affect oral drug absorption；
3. Exclusion of patients with symptomatic brain metastases or leptomeningeal metastasis; patients with brain metastases who have been treated and stabilized (with no progression within 4 weeks) may be included, but brain metastases cannot be used as target lesions；
4. Known invasive malignancies within the past 5 years that are still progressing or require active treatment (excluding patients with basal cell carcinoma, squamous cell carcinoma of the skin, or breast ductal carcinoma in situ or cervical carcinoma in situ who have received curative treatment)；
5. Previous immune therapy resulting in grade 3 or higher adverse events； Diagnosed with immunodeficiency or receiving long-term systemic corticosteroid treatment (prednisone equivalent dose >10 mg daily) or any form of immunosuppressive therapy within 7 days before the first dose of study treatment；
6. Active autoimmune diseases requiring systemic treatment (e.g., using disease-modifying drugs, corticosteroids, or immunosuppressive drugs) within the past 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-IV congestive heart failure (CHF) or a history of NYHA Class III or IV CHF；
10. Known history of human immunodeficiency virus (HIV) infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; Adebrelimab (PD-L1 inhibitor) 1200 mg on Day 1, every 3 weeks. Radiotherapy (SBRT) with a dose of 24Gy/3 fractions within 3 weeks after the first immunotherapy dose. UDCA 250 mg twice daily, starting 7 days before radiotherapy and continuing for 1 month after radiotherapy completion.	Drug: Ursodeoxycholic Acid (URSO); UDCA 250 mg twice daily, starting 7 days before radiotherapy and continuing for 1 month after completion.; Radiation: Radiotherapy; Radiotherapy (SBRT) with a dose of 24Gy/3 fractions within 3 weeks after the first immunotherapy dose.; Drug: Adebrelimab (PD-L1 inhibitor); Adebrelimab (PD-L1 inhibitor) 1200 mg on Day 1, every 3 weeks.
Active Comparator: Control Group; Adebrelimab 1200 mg on Day 1, every 3 weeks. Radiotherapy (SBRT) with a dose of 24Gy/3 fractions within 3 weeks after the first immunotherapy dose.	Radiation: Radiotherapy; Radiotherapy (SBRT) with a dose of 24Gy/3 fractions within 3 weeks after the first immunotherapy dose.; Drug: Adebrelimab (PD-L1 inhibitor); Adebrelimab (PD-L1 inhibitor) 1200 mg on Day 1, every 3 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) of lesions outside the radiotherapy field, assessed by RECIST 1.1 criteria.	From date of randomization to 4 weeks after completion of radiotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease Control Rate (DCR) of lesions outside the radiation field, assessed by RECIST 1.1 criteria	From date of randomization to 4 weeks after completion of radiotherapy
Safety: Incidence of Grade ≥3 toxicities, assessed by CTCAE 5.0 criteria	From first dose of study drug to 30 days post-treatment completion
Objective Response Rate (ORR) of lesions within the radiation field, assessed by RECIST 1.1 criteria	From date of randomization to 4 weeks after completion of radiotherapy
Overall response assessment of lesions both within and outside the radiation field, assessed by mRECIST criteria	From date of randomization to 4 weeks after completion of radiotherapy
Progression-Free Survival (PFS): Time from randomization to the first documented progression or death, whichever occurs first	From randomization to the first documented progression or death, whichever occurs first, assessed every 6 weeks up to 48 weeks post-randomization.
Overall Survival (OS): time from randomization to death from any cause	From randomization to death from any cause, assessed continuously until all patients have died (up to 5 years post-randomization).

Other Outcome Measures

Outcome Measure	Time Frame
Circulating Tumor Cells (CTCs) Enumeration	Within 1 week before radiotherapy, within 1 week after the completion of radiotherapy
Circulating Tumor DNA (ctDNA)	Within 1 week before radiotherapy, within 1 week after the completion of radiotherapy
Peripheral Blood Mononuclear Cell (PBMC) Immune Composition	Within 1 week before radiotherapy, within 1 week after the completion of radiotherapy
Whole Blood Immune Factor Profiling	Within 1 week before radiotherapy, within 1 week after the completion of radiotherapy

Collaborators and Investigators

• Sponsor: Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 12, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 19, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Cholagogues and Choleretics; Immune Checkpoint Inhibitors; Ursodeoxycholic Acid
• Other Study ID Numbers: NCC5137；Approve No.25/004-0004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No