Combining TIL therapy and immunotherapy for advanced breast cancer

Efficacy and Safety of Autologous Tumor-Infiltrating Lymphocytes (TIL) Therapy Combined With Pembrolizumab (Keytruda) Immunotherapy in Patients With Advanced or Metastatic Refractory Breast Cancer

This study is testing a new treatment that combines a special type of immune cell therapy with a drug called Pembrolizumab to see if it can help people with advanced breast cancer.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 85 (estimated)
• Ages: 16 Years to 90 Years
• Sex: All
• Sponsor: Essen Biotech (other)
• Drugs / interventions: chemotherapy, immunotherapy, Prednisone, Pembrolizumab, cyclophosphamide, fludarabine
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06532812 on ClinicalTrials.gov

What this trial studies

This Phase I/II study evaluates the safety and efficacy of autologous tumor-infiltrating lymphocytes (TIL) therapy combined with Pembrolizumab (Keytruda) in patients with advanced or metastatic refractory breast cancer. The process involves harvesting TILs from patients' tumors, expanding them in vitro, and infusing them back into the patients after a lymphodepletion regimen. Pembrolizumab is administered to enhance the immune response against the tumor. The primary goal is to determine the objective response rate (ORR), with secondary endpoints including disease control rate, progression-free survival, overall survival, duration of response, and quality of life.

Who should consider this trial

Good fit: Ideal candidates include patients aged 16 to 90 with histologically diagnosed advanced or metastatic breast cancer who have failed standard treatment regimens.

Not a fit: Patients with early-stage breast cancer or those who have not yet undergone standard treatment options may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a novel, personalized treatment option for patients with limited therapeutic alternatives for advanced breast cancer.

How similar studies have performed: Other studies have shown promise with similar approaches combining TIL therapy and immunotherapy, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Age: 16 years to 90 years
* Histologically diagnosed as primary/relapsed/metastasized Breast Cancer
* Expected life span more than 3 months
* Karnofsky≥60% or ECOG score 0-2
* Test subjects have failed standard treatment regimens, or there are no standard treatment regimens available.
* Test subjects must have tumor regions eligible for biopsy or resection, or malignant body fluid where TILs can be isolated
* At least 1 evaluable tumor lesion
* Hematology and Chemistry（within 7 days prior to enrollment）:
* Absolute count of white blood cells≥2.5×10\^9/L
* Absolute count of neutropils≥1.5×10\^9/L
* Absolute count of lymphocytes ≥0.7×109/L
* Platelet count≥100×10\^9
* hemoglobin≥90 g/L
* Activated partial thromboplastin time (APTT) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
* International normalized ratio (INR) ≤1.5xULN (Unless received anticoagulant therapy within the previous 3 days)
* Serum creatinine ≤1.5mg/dL(or ≤132.6μmol/L), or clearance rate≥50mL/min
* Serum ALT/AST ≤3×ULN(subjects with liver metastasis ≤3×ULN)
* Totol bilirubin≤1.5×ULN
* No absolute or relative contraindications to operation or biopsy
* Test subjects with child-bearing potential must be willing to practice approved highly effective methods of contraception at the time of informed consent and continue within 1 year after the completion of lymphodepletion
* Any malignant tumor-targeting therapies, including radiotherapy, chemotherapy, and biologics must cease 28 days before obtaining TILs
* Be able to understand and sign the informed consent document;
* Be able to stick to follow-up visit plan and other requirements in the agreement.

Exclusion Criteria:

* Need glucocorticoid treatment, and daily dose of Prednisone greater than 15mg (or equivalent doses of hormones) or outoimmune diseases requiring immunomodulatory treatment
* Forced expiratory volume in one second (FEV1) less than 2L, diffusing capacity of the lung for carbon monoxide (DLCO) (calibrated) less than 40%
* Significant cardiovascular anomalies according to any of the following definitions:
* New York Heart Association (NYHA) Grade III or IV congestive heart failure, clinically significant
* Low blood pressure, uncontrollable symptomatic coronary artery diseases, or ejection fraction less than 35%; Severe cardiac rhythm and conduction anomaly, such as ventricular arrhythmia requiring clinical intervention, second-third degree atrioventricular conductive block, etc.
* Human immunodeficiency virus (HIV) infection or anti-HIV antibody positive, active HBV or HCV infection (HBsAg positive and/or anti-HCV positive), syphilis infection or Treponema pallidum antibody positive.
* Severe physical or mental diseases;
* Have a systemic active infection requiring treatment, or have positive blood cultures(or imaging evidence of infection).
* Having been treated within a month or being treated now with other medicines, or other biologic therapy, chemo-or radiotherapy.
* History of allergy to chemical compounds consisting of chemical and biological substances resembling cell therapy.
* Having received immunotherapy and developed an irAE level greater than Level 3.
* Previous anti-tumor treatment AE did not return to CTCAE5.0 version grade 1 or below (toxicity considered by the investigator as non-safety concerns like alopecia excluded).
* Females in pregnancy or lactation. History of organ transplantation, allogeneic stem cell transplantation, and renal replacement therapy.
* Researchers consider the test subject as having a history of other severe systemic diseases, or other reasons inappropriate for the clinical study.

Where this trial is running

Beijing, Beijing Municipality

• District One Hospital — Beijing, Beijing Municipality, China (RECRUITING)

Study contacts

• Study coordinator: Rhoda M Smith, Phd

Conditions: Breast Cancer, Breast Carcinoma, Breast Cancer Metastatic, Breast Cancer Triple Negative, Tumor Infiltrating Lymphocytes, CAR-T CELL, Biological Therapy, CAR-T