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

NCT06842472 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: NCC5137；Approve No.25/004-0004
• Study Type: interventional
• Target: 70
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• 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.

Other Outcomes (4)

• 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

Study Arms (2)

Experimental Group

EXPERIMENTAL

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); Radiation: Radiotherapy; Drug: Adebrelimab (PD-L1 inhibitor)

Control Group

ACTIVE COMPARATOR

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; Drug: Adebrelimab (PD-L1 inhibitor)

Interventions

Ursodeoxycholic Acid (URSO) DRUG

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

Experimental Group

Radiotherapy RADIATION

Radiotherapy (SBRT) with a dose of 24Gy/3 fractions within 3 weeks after the first immunotherapy dose.

Control Group; Experimental Group

Adebrelimab (PD-L1 inhibitor) DRUG

Adebrelimab (PD-L1 inhibitor) 1200 mg on Day 1, every 3 weeks.

Control Group; Experimental Group

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years；
• Patients with recurrent/metastatic HER2-negative breast cancer；
• Patients who have previously received standard treatment regimens for recurrent/metastatic breast cancer；
• At least one lesion suitable for radiation therapy；
• 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；
• ECOG performance status of 0-2；
• Signed informed consent；
• Patients who have previously received radiation therapy may be included as long as it does not interfere with irradiation of the target lesion；

You may not qualify if:

• Biliary obstruction, acute or chronic cholecystitis or cholangitis, or long-term biliary colic (contraindication for UDCA)；
• 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；
• 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)；
• 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；
• Active autoimmune diseases requiring systemic treatment (e.g., using disease-modifying drugs, corticosteroids, or immunosuppressive drugs) within the past 2 years；
• Active infections requiring systemic treatment；
• Known history of active tuberculosis；
• 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；
• Known history of human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

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

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ursodeoxycholic Acid; Radiotherapy; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycholic Acid; Cholic Acids; Bile Acids and Salts; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Cholanes; Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Min Deng, Doctor

CONTACT

13661135602; 923791362@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof

Study Record Dates

• First Submitted: February 12, 2025
• First Posted: February 24, 2025
• Study Start: February 1, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 24, 2025

Record last verified: 2025-02