Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes as Neoadjuvant Therapy for HER2-Negative Breast Cancer

Recruiting now · Phase 1/Phase 2

Conditions studied: Breast Neoplasms

In brief

RATIONALE: Patients with HER2-negative breast cancer not responding to initial neoadjuvant chemotherapy might have lower chances for a pathologic complete response (pCR) at definitive surgery, indicating worse prognosis. Adoptive cell therapy has demonstrated efficacy in advanced breast cancer, but whether the addition of adoptive cell therapy to neoadjuvant chemotherapy could increase the pCR rate remains unclear. Tumor-draining lymph node-derived lymphocytes (LNLs) that have abundant tumor-reactive T cells, but not exhausted T cells, are easy to produce. It is not yet known whether LNL treatment is safe and effective in patients with HER2-negative breast cancer not responding to neoadjuvant chemotherapy. PURPOSE: This open-label phase I/II trial is to investigate the safety and efficacy of autologous LNL in patients with HER2-negative breast cancer not responding to neoadjuvant chemotherapy.

Key facts

Study ID

NCT05981014

Run by

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

People needed

196

Starts

2023-08-01

Expected to finish

2035-05-31

Last updated by the study team

2023-08-08

Who can join

Age: 18 and older, up to 70. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• In order to be eligible for participation in this trial, the participant must:
• Have signed the informed consent to study participation.
• Be a female subject and aged between 18 and 70 years.
• Provide a core needle biopsy which is histologically confirmed as invasive breast cancer. Excisional biopsy or surgical biopsy is not allowed.
• Have received two cycles of doxorubicin or epirubicin, plus cyclophosphamide, and had stable disease (SD) confirmed by breast MRI.
• Have breast cancer defined as the following combined primary tumor (T), regional lymph node (N), and distant metastasis (M) staging per AJCC for breast cancer staging criteria version 8 based on breast MRI assessment:
• The minimum size of the primary tumor was 1 cm in largest diameter by breast MRI, N0-3, M0.
• Have HER2-negative breast cancer, defined as 0-1+ by immunohistochemistry or 2+ by immunohistochemistry without HER2 amplification by FISH.
• Have known hormone receptor status (estrogen receptor [ER], progesterone receptor [PgR]), Ki67 value and, if institutional standard permits, known tumor grade.
• Have not received prior therapies for breast cancer, including but not limited to, chemotherapy (except two cycles of doxorubicin or epirubicin, plus cyclophosphamide), radiotherapy, hormonal therapy, targeted therapy, biological therapy and surgery.
• Have accessible tumor-draining lymph nodes by surgery to grow LNL. Participants have not received sentinel lymph node biopsy (SLNB) and ipsilateral axillary lymph node dissection (ALND) for the breast cancer lesion.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Demonstrate adequate normal organ function:
• NOTE: Blood component or cytokine therapy is not allowed within 14 days before surgery.
• Routine blood test:
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L
• Lymphocyte count (LC) >0.5×10\^9/L
• Platelets (PLT) ≥100×10\^9/L
• Hemoglobin (Hb) ≥90 g/L
• Liver function test:
• AST and ALT ≤2.5 ×ULN (≤5×ULN for participants with liver metastases)
• ALP ≤2.5 ×ULN (≤5×ULN for participants with liver or bone metastases)
• Total bilirubin ≤1.5×ULN (≤3.0 mg/dL for participants with Gilbert's syndrome)
• Renal function test:
• Calculated creatinine clearance (CrCL) ≥45 mL/min OR creatinine ≤1.5 × ULN

You may not qualify if…

• The participant must be excluded from participating in this trial if the participant:
• Has metastatic breast cancer.
• Has a known additional malignancy within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, in situ cervical cancer, and ductal carcinoma in situ that has undergone radical mastectomy.
• Has a known history of cardiovascular disease, including but not limited to, (1) congestive heart failure (New York Heart Association [NYHA] functional classification Class > 2), (2) unstable angina pectoris, (3) myocardial infarction in the past 3 months, (4) supraventricular arrhythmia or ventricular arrhythmia that requires treatments.
• Has interstitial pneumonia or active pneumonia that has clinical implications, or other respiratory diseases that seriously affect pulmonary function.
• Has an active infection requiring systemic therapy or has an unexplained fever of >38.5℃ except fevers caused by cancer.
• Has arterial and/or venous thrombotic events in the past 5 months, e.g., cerebrovascular accident, deep vein thrombosis or pulmonary embolism.
• Has a known psychiatric, alcohol abuse or substance abuse disorders.
• Is pregnant or breastfeeding.
• Has an active autoimmune disease, a history of autoimmune disease, or autoimmune disease that has required systemic treatment (e.g., with use of prednisone at a dose of >10mg per day or other corticosteroids at an equivalent dose). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is allowed.
• Has a history of congenital immunodeficiency or acquired immunodeficiency (e.g., positive serology test for HIV).
• Has tuberculosis in the past one year, or has a history of active tuberculosis more than one year but did not receive regular treatments.
• Has known active hepatitis B or hepatitis C. Participants that are hepatitis B surface antigen (HBsAg) or hepatitis B core antigen (HBcAg) positive may participate provided that the HBV DNA level is normal. Participants that are hepatitis C antibody positive may participate provided that the HCV DNA level is normal. Carriers of HBV or HCV must receive anti-virus therapy, and take regular DNA copy number tests during this trial.
• Has received a live vaccine within 4 weeks prior to enrollment, or plans to receive a live vaccine during this trial.
• Has a history of allogeneic bone marrow or organ transplant.
• Has received the study-related drugs including anthracycline, cyclophosphamide, taxane, fludarabine, interleukin-2, except two cycles of doxorubicin or epirubicin, plus cyclophosphamide.
• Has a history of hypersensitivity or allergy to the drugs in this study and any of their components including but not limited to, LNL, doxorubicin/epirubicin, cyclophosphamide, nab-paclitaxel, fludarabine, interleukin-2, dimethyl sulphoxide (DMSO), human serum albumin (HSA), dextran-40 and antibiotics (β-lactam antibiotics, gentamicin).
• Has contraindication for use of IL-2, including but not limited to, refractory or intractable epilepsy, and active gastrointestinal bleeding.
• Has a history of Grade≥2 neuropathy.
• Has received long half-life angiogenesis inhibitors within four weeks prior to enrollment, e.g., bevacizumab.
• Is receiving any medication prohibited in combination with study treatments as described in the respective product labels, unless medication was stopped within 7 days prior to enrollment.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with participation for the full duration of the study, or render study participation not compatible with the participant's best interest, in the opinion of the investigator.

Where it is running

• Sun Yat-sen Memorial Hospital, Sun Yat-sen University — Guangzhou, Guangdong, China (enrolling)

Full record on ClinicalTrials.gov

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