A Single-Arm, Single-Center, Phase II Clinical Study of Camrelizumab Combined With Radiochemotherapy as Neoadjuvant Therapy for Early-Stage Triple-Negative Breast Cancer

A Single-Arm, Single-Center, Phase II Clinical Study of Camrelizumab Combined With Radiochemotherapy as Neoadjuvant Therapy for Early-Stage Triple-Negative Breast Cancer

Camrelizumab + Chemoradiotherapy for Early TNBC Sponsor/Leading Center: Tianjin Medical University Cancer Institute and Hospital Study Type: Single-arm, single-center, Phase Ⅱ clinical study Planned Enrollment: 43 patients Eligible Population 18-75-year-old female patients with newly diagnosed, untreated early invasive triple-negative breast cancer (TNBC) (ER-/PR-/HER2- per ASCO/CAP guidelines), clinical stage cT1c-T4d (any cN); central assessment of Ki67 and sTIL values, at least one measurable lesion (RECIST 1.1), normal major organ function, expected survival ≥3 months; negative pregnancy test (women of childbearing potential) with agreement to effective contraception; signed informed consent and good compliance.

Exclusion: Metastatic/bilateral/inflammatory TNBC; prior anti-tumor/PD-1/PD-L1 treatment within 12 months; active other malignancies, autoimmune diseases, interstitial lung disease, uncontrolled severe infections/heart disease; pregnancy/lactation; allergy to study drugs.

Study Design Treatment Regimen (Neoadjuvant + Individualized Follow-up)

All patients receive the same combined therapy, followed by surgery (with extended treatment for non-responders):

12-week core neoadjuvant treatment: Camrelizumab (200mg IV, Q3W) + nab-paclitaxel (100mg/m² IV, weekly) + carboplatin (AUC=1 IV, weekly) + SBRT (10Gy × 2 sessions, on the 3rd day after chemotherapy in Week 3 and 6).

Post-12-week evaluation & treatment:

Clinical responders: Undergo surgery within 3 weeks. Clinical non-responders: Continue with 12-week EC regimen (epirubicin 80mg/m² + cyclophosphamide 600mg/m², IV Q3W, 4 cycles) + camrelizumab, then surgery within 3 weeks.

Study Procedures Screening (≤28 days): Complete imaging, laboratory and physical examinations to confirm eligibility.

Treatment period: Scheduled combined therapy with regular efficacy assessments (breast imaging every 2 cycles) and safety monitoring.

Follow-up: Mandatory surgery after treatment; 90-day safety follow-up post-last dose, and long-term survival follow-up (q3m for Year 1, q6m thereafter) for 5 years.

Primary Outcome Pathological complete response (pCR, defined as ypT0/Tis ypN0: no residual invasive cancer in resected breast and sampled lymph nodes).

Inclusion Criteria:

• Female patients aged ≥18 years and ≤75 years with treatment-naive breast cancer;
• Histopathologically confirmed early-stage triple-negative invasive breast cancer as defined by the latest ASCO/CAP guidelines, meeting all of the following criteria: Pathological subtype must be triple-negative, specifically: ER-negative: IHC <1%, PR-negative: IHC <1%, HER2-negative: IHC 0/1+ or IHC 2+ but ISH-negative;
• Primary triple-negative breast cancer patients with clinical staging cT1c-T4d and any cN status;
• Center-assessed Ki67 and sTIL values;
• Expected survival ≥ 3 months;
• At least one measurable lesion present per RECIST 1.1 criteria;
• Organ function levels must meet the following requirements: 1) Complete blood count (CBC) neutrophil count (ANC) ≥ 1.5 × 10⁹/L (no hematopoietic growth factor use within 14 days prior to first study dose); White blood cell count (WBC) ≥3.0×10⁹/L and ≤15×10⁹/L; lymphocyte count (LC) ≥0.5×10⁹/L; platelet count (PLT) ≥100×10⁹/L (no blood transfusion within 14 days prior to first study dose) Hemoglobin (Hb) ≥90 g/L; 2) Blood Biochemistry: TBIL ≤1.5×ULN; ALT and AST ≤2.5×ULN; ALP ≤2.5×ULN; BUN and Cr ≤1.5×ULN with creatinine clearance ≥50 mL/min (Cockcroft-Gault formula); INR and APTT ≤ 1.5×ULN (without anticoagulant therapy); Thyroid-stimulating hormone (TSH) ≤ upper limit of normal (ULN); if abnormal, assess T3 and T4 levels; inclusion permitted if T3 and T4 levels are normal; 3) Cardiac function: Echocardiogram: LVEF ≥ 50%; Lead ECG: QT interval, females < 470 ms.
• Contraception: Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to first dosing and agree to use a medically approved highly effective contraceptive method during the study and for 90 days after the last study drug administration. The investigator or designated personnel will select an appropriate contraceptive method for the subject and her partner from the options below after consultation, confirming the subject understands how to use it correctly and consistently. At the timepoints listed in the protocol, the investigator will notify the subject of the need for continuous, correct contraception. Additionally, the subject must be aware that they must immediately notify the investigator if they discontinue the selected contraceptive method or if they suspect or confirm pregnancy. A highly effective contraceptive method is one that, when used correctly and consistently alone or in combination with other methods, has an annual failure rate of less than 1%. These include the following: 1) Correct placement of an intrauterine device (IUD). 2) Condoms used in combination with a spermicide (i.e., foam, gel, film, cream, or suppository). 3) Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusion surgery (occlusion confirmed effective by relevant instrumentation). 4) Male vasectomy.
• Voluntarily enrolled in this study, signed informed consent, demonstrated good compliance, and agreed to participate in follow-up visits.

Exclusion Criteria:

• Tumor-Related Symptoms and Treatments

  1. Patients with metastatic breast cancer or bilateral breast cancer;
  2. Patients with inflammatory breast cancer;
  3. Received any antitumor therapy within 12 months prior to signing the informed consent form, including chemotherapy, targeted therapy, radiotherapy, endocrine therapy, immunotherapy, biological therapy, or tumor embolization;
  4. Previous treatment with PD-1/PD-L1 antibodies, CTLA-4 antibodies, or other PD-1/PD-L1 inhibitors;

• Concurrent Diseases/Medical History

  1. Active malignancies within 5 years prior to or concurrent with informed consent. Patients with cured localized tumors such as basal cell carcinoma, squamous cell carcinoma of the skin, superficial bladder cancer, or cervical carcinoma in situ may be eligible.
  2. Major non-breast cancer-related surgical procedures within 4 weeks prior to enrollment, or patients not yet fully recovered from such procedures (tissue biopsies for diagnostic purposes and peripheral intravenous catheter placement for central venous access [PICC] are permitted);
  3. Subjects with any known or suspected autoimmune disease, except:

Hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy; Subjects with stable, well-controlled type 1 diabetes mellitus; 4) Presence of interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic disease (e.g., diabetes mellitus, pulmonary fibrosis, acute pneumonia); 5) History of live attenuated vaccine administration within 28 days prior to first study dose or anticipated live attenuated vaccine administration during the study period; 6) Human Immunodeficiency Virus (HIV) infection or known Acquired Immunodeficiency Syndrome (AIDS); Hepatitis B Virus Surface Antigen (HBsAg) positive, or Hepatitis B Core Antibody (HBcAb) positive followed by positive HBV-DNA test (HBV-DNA testing only for HBsAg negative and HBcAb positive patients) ; positive HCV-RNA test following positive HCV antibody test (HCV-RNA testing only performed in HCV antibody-positive patients); autoimmune hepatitis; 7) Severe infection within 4 weeks prior to first dosing, including but not limited to bacteremia requiring hospitalization, severe pneumonia, etc.; or active infection of CTCAE ≥ Grade 2 requiring systemic antibiotic treatment within 2 weeks prior to first dosing; or unexplained fever >38.5°C during screening/prior to first dosing (fever attributable to tumor may be acceptable for enrollment at investigator's discretion) ; evidence of active tuberculosis infection within 1 year prior to dosing; 8) Subjects with a history of or scheduled for allogeneic bone marrow transplantation or solid organ transplantation; 9) Peripheral neuropathy ≥ Grade 2; 10) Severe cardiac disease or discomfort, including but not limited to: History of heart failure or systolic dysfunction (LVEF < 50%); high-risk uncontrolled arrhythmias such as atrial tachycardia; resting heart rate >100 bpm; significant ventricular arrhythmias (e.g., ventricular tachycardia) or higher-degree atrioventricular block (i.e., Mobitz II second-degree AV block or third-degree AV block); coronary artery disease requiring antianginal medication; clinically significant valvular heart disease; ECG evidence of transmural myocardial infarction; poorly controlled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg);

• Treatment-Related Exclusions

  ① Subjects who received systemic immunostimulatory agents (including but not limited to interferon or interleukin-2, including investigational immunostimulants) within 4 weeks prior to the first dose;

  ② Subjects who received systemic immunosuppressive therapy (including but not limited to glucocorticoids, azathioprine, methotrexate, thalidomide, anti-tumor necrosis factor agents) within 2 weeks prior to the first dose. Excludes intranasal or inhaled corticosteroids or physiologically dosed systemic steroids (i.e., physiologically dosed corticosteroids not exceeding 10 mg/day of prednisone or equivalent);

  ③ Known allergy to the study drug or any of its excipients; or history of severe allergic reactions to other monoclonal antibodies;

• Pregnant or lactating women; women of childbearing potential with a positive baseline pregnancy test; or women of childbearing potential unwilling to use effective contraception throughout the study period.

• History of established neurological or psychiatric disorders, including epilepsy or dementia; subjects with known history of psychiatric drug abuse, alcoholism, or substance abuse;

• Any other condition deemed by the investigator to make the patient unsuitable for participation in this study.