Safety and Efficacy of an Autologous Tumor Infiltrating Lymphocyte (TIL) Therapy in Patients with Advanced Solid Tumors

Обзор

Multicenter, single arm, non-randomized, prospective, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (BEN101) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent and/or metastatic solid tumor.

Подробное описание

BEN101 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process, for the treatment of patients with recurrent and/or metastatic solid tumor. The cell transfer therapy used in this study involves patients receiving a NMA lymphocyte depleting preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.

Вмешательства

• Биопрепарат BEN101
  Lymphodepletion regimen：Cyclophosphamide 250mg/ m2/day x 3 days (day -4, -3，-2) , Fludarabine 25mg/ m2/day x 2 days (day-4, -3) , Paclitaxel 100mg/ m2/day -3. The lymphodepletion regimen could be adjusted by the treating physician according to patient's disease condition. BEN101 infusion： Single dose level between 1x10\^9 to 1x 10\^11，not lower than 1×10\^9 cells, final dose is affected by the starting amount of TILs cells isolated from the tumor tissue sample. IL-2：Administer 8-16 hr after TI

Первичные конечные точки

• Adverse Events (AE) [Срок оценки: 6 month]

Вторичные конечные точки (5)

• Objective Response Rate (ORR) [Срок оценки: Up to 24 months]
• Disease Control Rate (DCR） [Срок оценки: Up to 24 months]
• Duration of response (DOR) [Срок оценки: Up to 24 months]
• Progression free survival (PFS) [Срок оценки: Up to 24 months]
• Overall survival (OS) [Срок оценки: Up to 24 months]

Критерии участия

Критерии включения

• Be able and willing to provide written informed consent, and to comply with all requirements of study participation (including all study procedures).
• Age: 18 - 75 years.
• Histological or cytological diagnosis of advanced metastatic solid tumors.
• Progression on standard therapy, or intolerance to, refusal or unable to benefit from standard therapy according to investigator's judgement.
• At least one resectable lesion (or aggregate of lesions) of a minimum 15 mm in diameter post-resection; or core biopsy (aggregate of around 1 gram or two 18G puncture needles).
• At least one measurable target lesion, as defined by RECIST v1.1.Lesions in previously irradiated areas (or other local therapy) should not be selected as target lesions, unless treatment was ≥ 3 months prior to screening, and there has been demonstrated disease progression in that particular lesion.
• ECOG performance status of 0 or 1.
• Life expectancy of at least 3 months.
• Adequate organ and marrow function (hematology, renal, hepatic and coagulation).

• Absolute neutrophil count (ANC) ≥ 1.0×10\^9/L.
• Hemoglobin (Hb) ≥ 80 g/L.
• Platelet ≥ 75×10\^9/L.
• Sufficient coagulation: APPT\<40 and INR\<1,5.
• Creatinine clearance (CrCL) ≥45 mL/min or serum creatinine ≤1.5mg/dL was estimated using the Cockcroft-Gault formula.
• Serum alanine transaminase (ALT)/ serum glutamic-pyruvic transaminase (SGPT) and aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) ≤ 3 times the upper limit of normal (ULN); patients with liver metastasis ≤ 5 times ULN.
• Estimated creatinine clearance (eCrCl) ≥ 40 mL/min using the Cockcroft-Gault formula.
• Total bilirubin ≤ 1.5 times ULN.
• Patients with Gilbert\'s syndrome must have a total bilirubin ≤ 1.5 times ULN.
• Patients with left ventricular ejection fraction (LVEF) ≥50% or New York Heart Association (NYHA) functional classification ≤ Class 1.
• Patients with pulmonary function test (forced expiratory volume in 1 second FEV1) ≥75%.

Критерии исключения

• Patients who have received an organ allograft or prior cell transfer therapy.
• Patients who have a history of hypersensitivity to any component or excipient of study drugs.
• Patients who have active central nervous system (CNS) metastases（except stable brain metastases without hormone dependence or drug treatment within 3 months before enrollment）.
• Patients who have active medical illness(es) that would pose increased risk for study participation, including: active systemic infections requiring systemic antibiotic therapy, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system.
• Active hepatitis C subjects (Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive), human immunodeficiency virus (HIV) antibody positive; syphilis primary screening antibody positive; untreated active hepatitis B subjects (hepatitis B surface antigen (HBsAg) positive, or hepatitis B core antibody (HBcAb) positive and peripheral blood HBV DNA quantitative test greater than ULN), hepatitis B subjects need to receive anti-HBV treatment during the study period.
• Previous history of immunodeficiency (any form, primary or acquired), current long-term use of systemic corticosteroids or other immunosuppressants. Patients receiving steroids as replacement therapy for adrenocortical insufficiency at ≤ 10 mg/day of prednisone or other steroid equivalent may be eligible.
• Patients who have had another primary malignancy within the previous 3 years (with the exception of carcinoma in situ of the breast, cervix, or bladder; localized prostate cancer; and non-melanoma skin cancer that has been adequately treated).
• Patients who have received a live or attenuated vaccine within 28 days before signing the informed consent.
• Received other cell therapy products in the past.
• History of Grade ≥3 immune mediated AE (including AST/ALT elevations that where considered drug related and cytokine release syndrome) that was considered related to prior immune modulatory therapy (eg, immune checkpoint inhibitors, co-stimulatory agents, etc.) and required immunosuppressive therapy.
• Patients who are pregnant or breastfeeding.
• Before enrollment, adverse event due to any previous treatment or surgery which had not recovered to ≤ Grade 1 (according to CTCAE V5.0); except: alopecia, peripheral neuropathy ≤ grade 2, events that remain stable during supportive therapy (such as stable hypothyroidism with hormone replacement therapy), or other events that have no safety risk as assessed by the investigator.
• Patients who do not consent to the use of medically approved contraceptive methods during the study.
• Patients whose cancer requires immediate attention or who in the investigator's judgement is not suitable to participate in this trial.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• RenJi Hospital — Шанхай
• Shanghai General Hospital — Шанхай
• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT05831033 · 101T1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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