Study of LN-145, Autologous Tumor Infiltrating Lymphocytes in the Treatment of Patients With Cervical Carcinoma

Prospective, multicenter, single-arm, open label, interventional study evaluating adoptive cell therapy (ACT) with autologous tumor infiltrating lymphocytes (TIL) infusion (LN-145) followed by IL-2 after a non-myeloablative (NMA) lymphodepletion preparative regimen for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma

Inclusion Criteria

• Inclusion Criteria: To be eligible for the study, patients must meet ALL of the following criteria prior to enrollment in the study: 1. Must be ≥ 18 years of age at the time of consent. 2. Must have recurrent, metastatic, or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix that is not amenable to curative treatment with surgery and/or radiation therapy and for which no other therapies are expected to have significant benefit, in the opinion of the Investigator. 3. Must have at least 1 lesion that is resectable for TIL generation. The resected TIL generating lesion(s) should yield at least 1.5 cm in diameter post-resection of tumor tissue. Following resection for TIL generation, must have a remaining measurable target lesion as defined by RECIST v1.1 4. Must have had at least 1 and no more than 3 prior systemic chemotherapeutic treatments (such as carboplatin/cisplatin, paclitaxel, and bevacizumab except where there are contraindications) for cervical carcinoma. Patients must have progressive disease while receiving or after the completion of the most recent prior treatment. 5. Any prior therapy directed at the malignant tumor must be discontinued at least 28 days prior to tumor resection. Radiation therapy may have been received up to 28 days prior to tumor resection for lesions not expected to be used for TIL generation or target lesions. 6. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Patients must be seronegative for the human immunodeficiency virus (HIV). Patients with positive serology for hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), or hepatitis C virus (anti-HCV) indicating acute or chronic infection may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment. 8. Patients of childbearing potential must be willing to practice an approved method of birth control starting at the time of informed consent and for 1 year after the completion of the study treatment regimen. Exclusion Criteria: 1. Patients who have received an organ allograft or prior cell transfer therapy except for prior LN-145 therapy. 2. Patients who are on a systemic steroid therapy > 10 mg of prednisone daily or other steroid equivalent. 3. Patients who currently have prior therapy-related toxicities greater than Grade 1 according to NCI-CTCAE v4.03; except for peripheral neuropathy, alopecia, or vitiligo prior to enrollment/resection. 4. Patients who have a contraindication to or history of hypersensitivity reaction to any component or excipients of the TIL therapy and the other study drugs. 5. Patients with active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory, or immune system. 6. Patients with symptomatic and/or untreated brain metastases (of any size and any number). 7. Patients who have any form of primary or acquired immunodeficiency syndrome, such as severe combined immunodeficiency disease or acquired immune deficiency syndrome (AIDS). 8. Patients who have a diagnosis of end-stage renal disorder requiring hemodialysis. 9. Patients who have a left ventricular ejection fraction (LVEF) < 45% or who are New York Heart Association (NYHA) Class 2 or higher. 10. Patients who have a forced expiratory volume in 1 second (FEV1) of less than or equal to 60% of predicted normal. 11. Patients who have received a live or attenuated vaccine within 28 days of the NMA-LD regimen. 12. Patients whose cancer requires immediate treatment or who would otherwise suffer a disadvantage by participating in this study. 13. Patients who have received prior treatment with immunotherapy (eg, anti-PD-1 anti-PD-L1, or anti-CTLA4 antibodies)

LN-145 is an adoptive cell transfer therapy that utilizes an autologous TIL manufacturing process, as originally developed by the NCI, for the treatment of patients with recurrent, metastatic, or persistent cervical carcinoma. 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.

Lead Organization
Iovance Biotherapeutics, Inc.