The Optimal Radioimmunotherapy Combinations for Advanced TNBC

A Prospective, Multicenter Clinical Trial Exploring the Optimal Combination Strategies of Radiotherapy and Immunotherapy for Advanced Triple-Negative Breast Cancer

This study aims to explore the best combination patterns of radiotherapy and immunotherapy for advanced triple-negative breast cancer (TNBC).

Study Overview

• Status: Recruiting
• Conditions: Triple-Negative Breast Cancer (TNBC)
• Intervention / Treatment: Radiation: radiotherapy 5 Gy × 5 fractions, once a day; Drug: Toripalimab; Drug: chemotherapy regimen selected by the investigator; Radiation: radiotherapy 8 Gy × 5 fractions, once a day; Radiation: radiotherapy 8 Gy × 3 fractions, once every other day; Radiation: radiotherapy 10 Gy× 3 fractions, once every other day; Radiation: radiotehrapy 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (total 8Gy)

Detailed Description

Metastatic triple-negative breast cancer (mTNBC) is a particularly aggressive form of breast cancer that poses significant therapeutic challenges. Because mTNBC tumors do not express estrogen receptors (ER), progesterone receptors (PR), or HER2, patients with this subtype cannot receive benefits from endocrine therapy or HER2-targeted treatments, leaving chemotherapy as the main treatment option. However, the effectiveness of traditional chemotherapy drugs is limited and they often come with severe side effects. This leads to short durations of progression-free survival (PFS) and overall survival (OS), and the development of drug resistance, which can cause the cancer to recur and spread.

Recently, the advent of immune checkpoint inhibitors has offered new therapeutic prospects for mTNBC. Inhibitors of PD-1/PD-L1, such as Pembrolizumab, Atezolizumab, and Toripalimab, have demonstrated some effectiveness in clinical trials, especially in patients with PD-L1-positive tumors. Yet, the overall response to immunotherapy remains low, and there is a risk of immune-related adverse events (irAEs), which require vigilant monitoring.

To address the shortcomings of both chemotherapy and immunotherapy, researchers are investigating innovative treatment strategies. These include targeting additional immune checkpoint molecules within the tumor microenvironment, developing novel chemotherapy drugs, and integrating immunotherapy with other treatments like radiotherapy. Local radiotherapy can substantially stimulate the immune system, increasing the antigenicity of cancer cells and enhancing the ability of cytotoxic T lymphocytes to recognize and attack cancer cells.

Although combined radiotherapy and immunotherapy have shown promise in treating other types of cancer, the most effective combination patterns, optimal radiotherapy dosing schedules, and the most suitable patient groups for advanced breast cancer, particularly mTNBC, are not well defined. This study seeks to identify the best combinations of radiotherapy and immunotherapy for advanced breast cancer, with the aim of improving survival rates and setting new standards for treatment.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shusen Wang, MD; Phone Number: +86-02087342491; Email: wangshs@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Qiufan Zheng, MD; Phone Number: +8602087342491; Email: zhengqf@sysucc.org.cn
      • Contact: Email: wangshs@sysucc.org.cn
      • Principal Investigator: Shusen Wang, MD.

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Inoperable locally advanced/metastatic triple-negative breast cancer (defined as ER and PR <1%; and HER2 negative as IHC 0 or IHC 1+, or IHC 2+ but negative upon fluorescence in situ hybridization (FISH) testing). Patients with ER/PR ≤10% and deemed unsuitable for endocrine therapy by the investigator are also eligible.
2. No prior chemotherapy for advanced/metastatic disease.
3. ECOG PS score of 0 or 1.
4. Presence of 1 to 5 tumor lesions suitable for radiotherapy (individual lesion size between 0.5 and 5 cm, not limited to 1 to 2 organs).
5. At least one measurable lesion outside the radiation field that can be evaluated.
6. Suitable to receive one of the chemotherapy regimens chosen by the investigator: nab-paclitaxel or gemcitabine + carboplatin.
7. Patients with brain metastases are allowed if they do not require local therapy at enrollment or if the metastatic lesion is treated with the assigned radiotherapy regimen.
8. Patients who have previously received PD-1/PD-L1 therapy for early-stage disease are allowed to enroll.
9. Able to provide tumor tissue sections or agree to tumor biopsy during the screening period.

10. Adequate organ and bone marrow function, with specific requirements:

    1. Hematology: Neutrophil count (ANC) ≥1.5×10^9/L; Platelet count (PLT) ≥90×10^9/L; Hemoglobin (Hb) ≥90 g/L; No blood product transfusion (including red blood cell and platelet products, etc.) or growth factor (including colony-stimulating factors, interleukins, and erythropoietin, etc.) support treatment within 2 weeks prior to examination.
    2. Liver function: Serum total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5×ULN (for patients with liver metastases: ALT and AST ≤5×ULN).
    3. Renal function: Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance >60 mL/min.

Exclusion Criteria:

1. Received platinum-containing regimens during the adjuvant/neoadjuvant therapy phase, and the interval from the last treatment to recurrence/metastasis is less than 6 months.
2. Have received radiotherapy within 12 weeks prior to enrollment, unless the radiotherapy was for adjuvant purposes and there are lesions outside the previously irradiated field.
3. Extensive tumor metastasis with surrounding normal tissues that cannot tolerate radiotherapy damage.
4. Significant third-space fluid retention (e.g., ascites, pleural effusion, pericardial effusion).
5. Require long-term systemic corticosteroid treatment.
6. Have active autoimmune diseases.
7. Have concurrent severe infections.
8. Other patients deemed unsuitable for enrollment by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1: 5Gy × 5 , daily; within 4 weeks before the initiation of cycle of toripalimab and chemotherapy	Radiation: radiotherapy 5 Gy × 5 fractions, once a day; 5 Gy × 5 fractions, once a day, beginning on the day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy; Drug: Toripalimab; Toripalimab (240 mg IV, d1, Q3W); Drug: chemotherapy regimen selected by the investigator; Regimens to be selected from: (1) Nab-paclitaxel (125 mg/m2 IV, days 1, 8, Q3W) (2) Gemcitabine (1000 mg/m² IV, days 1 and 8, Q3W) + carboplatin (AUC=2 IV, days 1 and 8, Q3W)
Experimental: Arm 2: 8Gy × 5 , daily; within 4 weeks before the initiation of cycle of toripalimab and chemotherapy	Drug: Toripalimab; Toripalimab (240 mg IV, d1, Q3W); Drug: chemotherapy regimen selected by the investigator; Regimens to be selected from: (1) Nab-paclitaxel (125 mg/m2 IV, days 1, 8, Q3W) (2) Gemcitabine (1000 mg/m² IV, days 1 and 8, Q3W) + carboplatin (AUC=2 IV, days 1 and 8, Q3W); Radiation: radiotherapy 8 Gy × 5 fractions, once a day; 8 Gy × 5 fractions, once a day, beginning on the day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy
Experimental: Arm 3: 8Gy × 3, every other day; within 4 weeks before the initiation of cycle of toripalimab and chemotherapy	Drug: Toripalimab; Toripalimab (240 mg IV, d1, Q3W); Drug: chemotherapy regimen selected by the investigator; Regimens to be selected from: (1) Nab-paclitaxel (125 mg/m2 IV, days 1, 8, Q3W) (2) Gemcitabine (1000 mg/m² IV, days 1 and 8, Q3W) + carboplatin (AUC=2 IV, days 1 and 8, Q3W); Radiation: radiotherapy 8 Gy × 3 fractions, once every other day; 8 Gy × 3 fractions, once every other day, beginning on the day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy
Experimental: Arm 4: 10Gy × 3, every other day; within 4 weeks before the initiation of cycle of toripalimab and chemotherapy	Drug: Toripalimab; Toripalimab (240 mg IV, d1, Q3W); Drug: chemotherapy regimen selected by the investigator; Regimens to be selected from: (1) Nab-paclitaxel (125 mg/m2 IV, days 1, 8, Q3W) (2) Gemcitabine (1000 mg/m² IV, days 1 and 8, Q3W) + carboplatin (AUC=2 IV, days 1 and 8, Q3W); Radiation: radiotherapy 10 Gy× 3 fractions, once every other day; 10 Gy × 3 fractions, once every other day, beginning on the day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy
Experimental: Arm 5: 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (8 Gy in total); on the first 2 days of first 4 cycles of toripalimab and chemotherapy	Drug: Toripalimab; Toripalimab (240 mg IV, d1, Q3W); Drug: chemotherapy regimen selected by the investigator; Regimens to be selected from: (1) Nab-paclitaxel (125 mg/m2 IV, days 1, 8, Q3W) (2) Gemcitabine (1000 mg/m² IV, days 1 and 8, Q3W) + carboplatin (AUC=2 IV, days 1 and 8, Q3W); Radiation: radiotehrapy 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (total 8Gy); 0.5 Gy twice-a-day × 2 days, on the first 2 days of the first 4 cycles of toripalimab and chemotherapy (total 8Gy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival at 6 months (6m-PFS rate)	Progression-free survival at 6 months (6m-PFS rate) is defined as the percentage of patients who have not experienced disease progression or death due to any cause at the 6-month mark after starting treatment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS) is defined as the time from treatment initiation to disease progression or death from any cause.	Up to 3 years
Overall survival (OS)	Overall survival (OS) is defined as the time from treatment initiation to death from any cause.	up to 3 years
Objective Response Rate	Objective response rate (ORR) is defined as the percetage of patients achieving a complete response (CR) or partial response (PR) according to RECIST v.1.1.	up to 3 years
Duration of response	Duration of response (DOR) is defined as the duration from response initiation (when either CR or PR is first determined) to progression or death, whichever occurs first.	up to 3 years
Number of participants with treatment-related adverse events	Adverse events are assessed by CTCAE v5.0	up to 3 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: West China Hospital; First Affiliated Hospital Xi'an Jiaotong University

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: December 5, 2024
• First Submitted That Met QC Criteria: December 13, 2024
• First Posted (Actual): December 16, 2024

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: chemotherapy; immunotherapy; radiotherapy; triple-negative breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Skin and Connective Tissue Diseases; Triple Negative Breast Neoplasms; toripalimab
• Other Study ID Numbers: SYSUCC-025

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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