The Optimal Radioimmunotherapy Combinations for Advanced TNBC

NCT ID: NCT06735131

Last Updated: 2025-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-12-20

Study Completion Date

2027-01-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Triple-Negative Breast Cancer (TNBC)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: 5Gy × 5 , daily

within 4 weeks before the initiation of cycle of toripalimab and chemotherapy

Group Type EXPERIMENTAL

radiotherapy 5 Gy × 5 fractions, once a day

Intervention Type RADIATION

5 Gy × 5 fractions, once a day, beginning on the day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy

Toripalimab

Intervention Type DRUG

Toripalimab (240 mg IV, d1, Q3W)

chemotherapy regimen selected by the investigator

Intervention Type DRUG

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)

Arm 2: 8Gy × 5 , daily

within 4 weeks before the initiation of cycle of toripalimab and chemotherapy

Group Type EXPERIMENTAL

radiotherapy 8 Gy × 5 fractions, once a day

Intervention Type RADIATION

8 Gy × 5 fractions, once a day, beginning on the day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy

Toripalimab

Intervention Type DRUG

Toripalimab (240 mg IV, d1, Q3W)

chemotherapy regimen selected by the investigator

Intervention Type DRUG

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)

Arm 3: 8Gy × 3, every other day

within 4 weeks before the initiation of cycle of toripalimab and chemotherapy

Group Type EXPERIMENTAL

radiotherapy 8 Gy × 3 fractions, once every other day

Intervention Type RADIATION

8 Gy × 3 fractions, once every other day, beginning on the day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy

Toripalimab

Intervention Type DRUG

Toripalimab (240 mg IV, d1, Q3W)

chemotherapy regimen selected by the investigator

Intervention Type DRUG

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)

Arm 4: 10Gy × 3, every other day

within 4 weeks before the initiation of cycle of toripalimab and chemotherapy

Group Type EXPERIMENTAL

radiotherapy 10 Gy× 3 fractions, once every other day

Intervention Type RADIATION

10 Gy × 3 fractions, once every other day, beginning on the day within 4 weeks before the initiation of cycle of toripalimab and chemotherapy

Toripalimab

Intervention Type DRUG

Toripalimab (240 mg IV, d1, Q3W)

chemotherapy regimen selected by the investigator

Intervention Type DRUG

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)

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

Group Type EXPERIMENTAL

radiotehrapy 0.5Gy twice-a-day × 2 days, repeat for 4 cycles (total 8Gy)

Intervention Type RADIATION

0.5 Gy twice-a-day × 2 days, on the first 2 days of the first 4 cycles of toripalimab and chemotherapy (total 8Gy)

Toripalimab

Intervention Type DRUG

Toripalimab (240 mg IV, d1, Q3W)

chemotherapy regimen selected by the investigator

Intervention Type DRUG

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)

Interventions

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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

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type 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)

Intervention Type RADIATION

Toripalimab

Toripalimab (240 mg IV, d1, Q3W)

Intervention Type 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)

Intervention Type DRUG

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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West China Hospital

OTHER

Sponsor Role collaborator

First Affiliated Hospital Xi'an Jiaotong University

OTHER

Sponsor Role collaborator

Sun Yat-sen University

OTHER

Sponsor Role lead

Responsible Party

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wang shusen

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Shusen Wang, MD

Role: CONTACT

+86-02087342491

Facility Contacts

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Qiufan Zheng, MD

Role: primary

+8602087342491

Role: backup

Other Identifiers

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SYSUCC-025

Identifier Type: -

Identifier Source: org_study_id

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