Combined Chemo-immunotherapy Plus SBRT in Neoadjuvant Treatment for Luminal Subtype Breast Cancer

NCT07254858 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: KY2025-301
• Study Type: interventional
• Target: 302
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, randomized controlled clinical trial designed to evaluate the efficacy and safety of combining radiotherapy, chemotherapy, and immunotherapy in the neoadjuvant treatment of high-risk HR+/HER2- breast cancer patients. The study plans to enroll treatment-naïve HR+/HER2- breast cancer patients aged 18-75 with high-risk features (e.g., tumor size ≥3 cm or lymph node positivity, Ki-67 ≥20%). Eligible subjects will be randomized in a 1:1 ratio into two groups: the control group will receive neoadjuvant chemotherapy (nab-paclitaxel followed by epirubicin + cyclophosphamide) in combination with sintilimab immunotherapy; the experimental group will receive the same chemotherapy and immunotherapy regimen with the addition of stereotactic body radiotherapy (SBRT) administered early during treatment, at a prescribed dose of 8 Gy per fraction for 3 fractions, with one fraction per day. The study has dual primary endpoints: pathological complete response (pCR,) and objective response rate (ORR ). Secondary endpoints include 3-year event-free survival (EFS), incidence of adverse events (CTCAE v5.0), and postoperative cosmetic outcomes of the breast. The study design incorporates hierarchical testing to control for multiplicity, and long-term follow-up is planned to evaluate survival benefits. The study has been approved by the ethics committee, and all participants are required to provide written informed consent. The results are expected to offer a novel neoadjuvant treatment strategy for high-risk HR+/HER2- breast cancer patients and improve their therapeutic outcomes.

Conditions

HR+/HER2- Breast Cancer

Keywords

Breast Cancer; Radiotherapy; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Pathological complete response rate（pCR）

  Postoperative pathological assessment (tumor Miller-Payne system grading and axillary lymph node pathological assessment)

  Pathological diagnosis results were obtained tithin one month after the operation

Secondary Outcomes (3)

• Objective response rate(ORR)

  At the end of Cycle 8 (each cycle is 28 days)

• Event-free survival rate

  Long-term follow-up monitoring was conducted until 3 years after enrollment

• Incidence of adverse reactions

  1 year

Other Outcomes (1)

• The breast-conserving rate of breast malignant tumor surgery

  Perioperative/Periprocedural

Study Arms (2)

Chemotherapy+Immunotherapy

EXPERIMENTAL

Control Group: Neoadjuvant chemotherapy combined with immunotherapy, wherein the neoadjuvant chemotherapy regimen follows the clinical standard protocol. Neoadjuvant Chemotherapy Regimen: A sequential chemotherapy strategy is adopted, with the specific regimen as follows: Taxane-based Chemotherapy Phase (T Phase): Nab-paclitaxel (125 mg/m²), administered by intravenous infusion on Day 1 and Day 8 of each 21-day cycle (Q3W), for a total of 4 cycles. Anthracycline-based Combination Chemotherapy Phase (EC Phase): Epirubicin (75-100 mg/m²) in combination with cyclophosphamide (600 mg/m²), administered by intravenous infusion every 21 days (Q3W), for a total of 4 cycles. The EC phase commences upon completion of the T phase. Immunotherapy Regimen: Sintilimab (200 mg), administered by intravenous infusion every three weeks (Q3W). Dosing begins on Day 2 of the chemotherapy cycles, for a total of 8 treatment cycles.

Drug: Neoadjuvant Chemotherapy (NACT); Drug: Immunotherapy (Sintilimab)

Chemotherapy + Immunotherapy + Radiotherapy

EXPERIMENTAL

Neoadjuvant chemotherapy combined with immunotherapy（same as Arm1) + Neoadjuvant Radiotherapy

Radiation: Neoadjuvant radiotherapy; Drug: Neoadjuvant Chemotherapy (NACT); Drug: Immunotherapy (Sintilimab)

Interventions

Neoadjuvant radiotherapy RADIATION

Neoadjuvant Radiotherapy Regimen: 1. Radiotherapy Technique: Stereotactic Body Radiation Therapy (SBRT) Radiation Dose and Fractionation: 8 Gy per fraction, for a total of 3 fractions, amounting to a total dose of 24 Gy 2. Radiotherapy Schedule: Irradiation begins on the second day of the first chemotherapy cycle and is administered every other day 3. Target Volume Definition: The radiotherapy target volume is defined based on baseline imaging (e.g., CT, MRI, or PET-CT) 4. Radiotherapy Equipment and Planning: Treatment is delivered using a linear accelerator equipped with Image-Guided Radiotherapy (IGRT) technology to ensure precise irradiation and dose optimization

Chemotherapy + Immunotherapy + Radiotherapy

Neoadjuvant Chemotherapy (NACT) DRUG

Neoadjuvant Chemotherapy Regimen: A sequential chemotherapy strategy is adopted, with the specific regimen as follows: Taxane-based Chemotherapy Phase (T Phase): Nab-paclitaxel (125 mg/m²), administered by intravenous infusion on Day 1 and Day 8 of each 21-day cycle (Q3W), for a total of 4 cycles. Anthracycline-based Combination Chemotherapy Phase (EC Phase): Epirubicin (75-100 mg/m²) in combination with cyclophosphamide (600 mg/m²), administered by intravenous infusion every 21 days (Q3W), for a total of 4 cycles. The EC phase commences upon completion of the T phase.

Chemotherapy + Immunotherapy + Radiotherapy; Chemotherapy+Immunotherapy

Immunotherapy (Sintilimab) DRUG

Immunotherapy Regimen: Sintilimab (200 mg), administered by intravenous infusion every three weeks (Q3W). Dosing begins on Day 2 of the chemotherapy cycles, for a total of 8 treatment cycles.

Chemotherapy + Immunotherapy + Radiotherapy; Chemotherapy+Immunotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed, untreated breast cancer;
• Age: 18 years ≤ age ≤ 75 years;
• Histologically confirmed hormone receptor-positive (HR+) tumor specimen (estrogen receptor \[ER\] ≥ 10%);
• Human epidermal growth factor receptor-2 immunohistochemistry (HER2-IHC) result of 0/1+ or 2+ with negative fluorescence in situ hybridization (FISH) test;
• Histologically confirmed cell proliferation index (Ki67) ≥ 20%;
• Programmed death-ligand 1 combined positive score (PD-L1 CPS) evaluable (i.e., availability of fresh/archived specimens);
• Good pulmonary function;
• Adequate hepatic and renal function;
• Histological grade ≥ 2;
• cN0, cT ≥ 3 cm or cN1-3, cT ≥ 2 cm (cT: clinically assessed maximum diameter of primary tumor; cN: clinically assessed regional lymph node status);

You may not qualify if:

• Pregnancy; 2.Tumor \> 8 cm with skin ulceration; 3.History of thoracic radiotherapy or contraindications to radiotherapy; 4.Active autoimmune disease; 5.Prior use of PD-L1 antibody therapy; 6.De novo breast cancer; 7.There are factors that may significantly increase the risk of lung or cardiac toxicity related to radiotherapy, such as (1) maximum lung depth(MLD) \>3.2cm； (2) maximum heart distance(MHD) \<2.4cm。

Sponsors & Collaborators

• First Affiliated Hospital of Wenzhou Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Neoadjuvant Therapy; Immunotherapy; sintilimab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Combined Modality Therapy; Therapeutics; Immunomodulation; Biological Therapy

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: September 8, 2025
• First Posted: November 28, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2029
• Last Updated: November 28, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)