Patient case: 72-year-old male with melanoma; genetic feature: TP53 loss of function

Clinical trial: Study of LN-144, Autologous Tumor Infiltrating Lymphocytes, in the Treatment of Patients With Metastatic Melanoma

Summary: Prospective, 3-cohort interventional study evaluating autologous tumor infiltrating lymphocyte (TIL) infusion (LN-144) followed by IL-2 after a non-myeloablative chemotherapy preparative regimen for the treatment of patients with metastatic melanoma.

Detailed description: LN-144 is an autologous adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with metastatic melanoma. The cell transfer therapy used in this study involves patients receiving a lymphocyte depleting preparative regimen, followed by infusion of autologous TIL followed by the administration of a regimen of IL-2.

Eligibility: To be eligible for the study, patients must meet ALL of the following criteria prior to enrollment
  1. Patients must have measurable metastatic melanoma and at least one lesion that is resectable for TIL generation.
  2. Patients must have undergone at least one prior systemic treatment for metastatic melanoma.
  3. Patients must have either progressive disease or no response (i.e, no PR or CR) while receiving or after completion of most recent prior treatment.
  4. Patients must be greater than 18 years of age at the time of consent. Enrollment of patients greater than 65 years of age can be done after consultation with the Medical Monitor.
  5. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. In the opinion of the Investigator, patient must be capable of participating and completing study procedures.
  7. Patients of child bearing age or potential must be willing to practice birth control during treatment and for four months after receiving all protocol related therapy.
  8. Patients must have a serum absolute neutrophil count (ANC) greater than 1000/mm3, hemoglobin greater than 9.0 g/dL, and platelet count greater than 100,000/mm3.
  9. Patients must have a serum ALT/SGPT and AST/SGOT less than three times the upper limit of normal (<3x ULN), a calculated creatinine clearance of greater than 50 mL/min (>50 mL/min), and a total bilirubin less than or equal to 2 mg/dL (≤ 2 mg/dL). Patients with Gilbert's Syndrome must have a total bilirubin less than 3 mg/dL (<3 mg/dL).
  10. Patients must be seronegative for the HIV antibody, hepatitis B antigen, and hepatitis C antibody or antigen.
  11. Patients must be EBV viral capsid antigen (VCA) IgG positive and/or, Epstein Barr nuclear antigen (EBNA) IgG positive, and have no clinical evidence of active EBV infection.
  12. Patients must not have received systemic chemotherapy or immune therapy for 2 weeks (targeted therapy) and 4 weeks (all other anti-cancer therapy) at the time of enrollment, and there must be no intention of receiving any non-protocol systemic anti-cancer chemotherapy or immune therapy during the study period.
  13. Patients with documented Grade 2 or greater diarrhea or colitis as a result of previous treatment with ipilimumab, tremelimumab, anti-PD1 or anti-PD-L1 antibodies must have been asymptomatic for at least 6 months or had a normal colonoscopy post treatment, with uninflamed mucosa by visual assessment.
  14. Patients must have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an informed consent form (ICF) approved by an institutional review board (IRB), and agree to abide by the study restrictions and return to the site for the required assessments.
  15. Patients have provided written authorization for use and disclosure of protected health information.
  Exclusion Criteria
  Patients who meet ANY of the following criteria will be excluded from the study:
  1. Patients with melanoma of uveal/ocular origin
  2. Patients who have received prior cell transfer therapy which included a nonmyeloablative or myeloablative chemotherapy regimen (not applicable for patients in the retreatment Cohort 3).
  3. Patients who have three or more active brain metastases. Note: Patients with one or two untreated or inadequately treated brain lesions or three or more adequately treated brain metastases may be eligible. If lesions are symptomatic or greater than or equal to 1 cm each, these lesions must have been definitively treated and stable for one month. Brain metastases with significant edema or hemorrhage and metastases larger than 2 cm are excluded.
  4. Patients who are pregnant or breastfeeding.
  5. Patients who are on a systemic steroid therapy regimen defined as the need for chronic steroid use for at least seven or more days at a dose of greater than 10 mg of prednisone or equivalent per day.
  6. Patients who have active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced in the medical history by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
  7. Patients who have any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease and AIDS).
  8. Patients who have a history of severe immediate hypersensitivity reaction to IL-2, fludarabine, or cyclophosphamide.
  9. Patients who have a history of coronary revascularization or ischemic symptoms.
  10. Patients who have an estimated glomerular filtration rate (eGFR) less than 40 mL/min using the Cockcroft-Gault formula at Screening or have end-stage renal disorder requiring hemodialysis.
  11. Patients who have an LVEF less than 45%. (Older patients [60 - 70 years], must have received an echocardiogram within the previous 60 days demonstrating LVEF ≥ 45%).
  12. Patients who have a documented FEV1 (forced expiratory volume in one second) of less than or equal to 60%
  13. Patients who have had another primary malignancy within the previous three years (with the exception of carcinoma in situ of the breast, urothelial cancer in situ, and non-melanoma skin cancer that has been adequately treated).

Relevance to patient case: not relevant