innovaTIL-04, 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 participation: 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 3. At least one resectable lesion (or aggregate of lesions resected) of a minimum 1.5 cm in diameter post resection to generate TIL; surgical removal with minimal morbidity (defined as any procedure for which expected hospitalization is ≤ 3 days) 4. At least one measurable target lesion, as defined by RECIST v1.1 5. Must have had at least one and no more than three prior systemic chemotherapeutic treatments (such as carboplatin/cisplatin, paclitaxel, and bevacizumab except where there are contraindications) for cervical carcinoma 6. 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 7. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 8. 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 antibody (HCV Ab) indicating acute or chronic infection may be enrolled if the viral load by polymerase chain reaction (PCR) is undetectable with/without active treatment. 9. Patients of childbearing potential must be willing to take the appropriate precaution to avoid pregnancy for the duration of the study and practice an approved, highly effective method of birth control during treatment and for 12 months after receiving the last protocol-related therapy. 10. Prior to study Enrollment (tumor resection), patient must have documentation of radiological disease progression after the most recent therapy. 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 chronic systemic steroid therapy 3. Patients who currently have prior therapy-related toxicities > Grade 1 according to National Cancer Institute (NCI-) Common Terminology Criteria for Adverse Events (CTCAE) v4.03; except for peripheral neuropathy, alopecia, or vitiligo prior to Enrollment (tumor resection) 4. Patients who have a history of hypersensitivity to any component or excipient of LN-145 or other study drugs: • NMA-LD preconditioning regimen (cyclophosphamide, mesna, and fludarabine) 5. Patients who have active systemic infections, coagulation disorders or other active major medical illnesse(es) of the cardiovascular, respiratory, or immune system, including evidence in the medical history of urinary tract obstruction, a positive cardiac stress test, myocardial infarction, cardiac arrhythmia, obstructive or restrictive pulmonary disease, or other conditions that in the opinion of the Investigator would increase the risk of participation 6. Patients with symptomatic and/or untreated brain metastases (of any size and any number) • Patients with definitively treated brain metastases may be considered for Enrollment, and must be stable for ≥ 14 days prior to beginning the NMA-LD preconditioning regimen 7. Patients who have any form of primary immunodeficiency (such as severe combined immunodeficiency [SCID] or acquired immunodeficiency 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 documented forced expiratory volume in 1 second (FEV1) of ≤ 60% 11. Patients who have received a live or attenuated vaccine within 28 days prior to beginning NMA-LD preconditioning regimen. 12. Patients whose cancer requires immediate attention or who would otherwise suffer a disadvantage by participating in this study 13. Patients who have received prior treatment with immunotherapy (eg, anti-programmed cell death protein-1 [PD-1], anti-programmed death ligand 1 [PD-L1], or anti-cytotoxic T lymphocyte-associated antigen-4 [CTLA-4] antibodies) 14. Patients who have had another primary malignancy within the previous 3 years (except for curatively treated localized malignancy that has not required treatment for > 1 year, and in the judgement of the Investigator, does not pose a significant risk of recurrence including, but not limited to, non-melanoma skin cancer or bladder cancer) 15. Patients who have ≥ Grade 2 hemorrhage within 14 days prior to Enrollment (tumor resection)

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.