Phase I Study of Autologous Tumor-Draining Lymph Node-Derived Lymphocytes for Advanced HER2-Negative Breast Cancer

Recruiting now · Phase 1

Conditions studied: Breast Neoplasms

In brief

RATIONALE: Patients with HER2-negative advanced breast cancer have limited choice on targeted therapies, and often show only modest responses to available immunotherapies. Adoptive cell therapy with tumor-infiltrating lymphocytes has difficulties in preparing enough cells from solid tumors and overcoming the exhaustion and dysfunction of T cells, which limit its clinical use. Tumor-draining lymph node-derived lymphocytes (LNLs) that have abundant tumor-specific T cells, rather than exhausted T cells, are easier to produce. It is not yet known whether LNL treatment is safe and effective in patients with advanced HER2-negative breast cancer. PURPOSE: This phase I trial is mainly to study the safety of autologous LNL in patients with advanced HER2-negative breast cancer.

Key facts

Study ID

NCT06121557

Run by

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

People needed

24

Starts

2023-11-01

Expected to finish

2031-12-31

Last updated by the study team

2023-11-08

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.
• Have locally advanced or recurrent inoperable HER2-negative breast cancer (Stage IIIB\~IIIC) which cannot be treated with curative intent OR have metastatic breast cancer (Stage IV). HER2-negative breast cancer is defined by the most recent ASCO/CAP guidelines. Participants should appear clinically stable in the opinion of the investigator.
• Participants with estrogen receptor (ER)-positive and/or progesterone receptor (PR)-positive breast cancer have failed at least one line of hormonal therapy or CDK4/6 inhibitor, or are appropriate candidates for chemotherapy. Participants with ER-positive and/or PR-positive breast cancer may have received unlimited prior chemotherapy. Participants with triple-negative breast cancer (TNBC) may have received unlimited prior treatments for breast cancer.
• Have not received any prior adoptive cell therapy.
• Be suitable for treatment with camrelizumab and another anti-tumor drug chosen from chemotherapeutic drug, ADC, or PARP inhibitor as judged by the investigator.
• Have accessible tumor-draining lymph nodes by surgery to grow LNL.
• Have measurable disease based on RECIST 1.1. Target lesions situated in a previously irradiated area are considered measurable, only if they have shown unequivocal progression based on RECIST 1.1 after radiation therapy.
• Have provided recently or newly obtained biopsy from a locally advanced or recurrent inoperable or metastatic tumor lesion for pathological examination of molecular subtype and PD-L1 expression, unless contraindicated due to site inaccessibility and/or participant safety concerns.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have life expectancy ≥4 months.
• 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 rapidly progressing tumors, as judged by the investigator.
• Has known active CNS metastases and/or carcinomatous meningitis except for previously treated and radiographically stable CNS metastases, or CNS metastases without medication requirement and corticosteroid dependence. To demonstrate radiographic stability of brain metastases, a minimum of 2 post-treatment brain imaging assessments are required: (1) The first brain imaging must be acquired after treatment of brain metastases has been completed; (2) The second brain imaging must be obtained during screening and 4 weeks after the previous post-treatment brain imaging.
• Has spinal cord compression not relieved by surgery or radiotherapy. Participants with previously treated spinal cord compression may participate provided that the compression-related symptoms are relieved within more than one week prior to surgery for tumor-draining lymph nodes.
• Has uncontrolled pleural effusion, pericardial effusion or ascites. Participants with indwelling catheter may participate.
• Has uncontrolled cancer pain as judged by the investigator. Participants requiring pain medication must have a treatment plan before enrollment. Symptomatic lesions suitable for palliative radiotherapy should be treated before enrollment.
• Has a known additional malignancy that is progressing or requires active treatment within the last 5 years. Exceptions include basal or squamous cell carcinoma of the skin, and thyroid cancer that has undergone potentially curative therapy or in situ cervical cancer.
• 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 implication, 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.
• Is currently participating in a clinical study and receiving an investigational agent and/or using an investigational device, or has participated in a clinical study and received an investigational agent and/or used an investigational device within 4 weeks prior to enrollment.
• Note: Subjects who have entered the follow-up phase of a clinical study may participate as long as 4 weeks have elapsed since the last dose of the investigational agent and/or removal of the device.
• 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 >10 mg 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 a history of hypersensitivity or allergy to the drugs in this study and any of their components including but not limited to, LNL, cyclophosphamide, fludarabine, interleukin-2, dimethyl sulphoxide (DMSO), human serum albumin (HSA), dextran-40, antibiotics (β-lactam antibiotics, gentamicin), camrelizumab, or another anti-tumor drug that the investigator intends to choose.
• 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.
• Is receiving any medication prohibited in combination with study treatment as described in the respective product labels, unless medication was stopped within 7 days prior to enrollment.

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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