A phase 2 multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (LN-145) in patients with recurrent metastatic or persistent cervical carcinoma

Adoptive cell therapy (ACT) may be effective in treating immunogenic tumors with high mutational load, such as melanoma, and virally-associated tumors, like cervical cancer, with several patients in studies performed at various institutions achieving durable, complete responses for years. HPV infection increases mutational load, thus providing additional neoantigen targets ideal for the polyclonal nature of ACT. As outcomes for patients with recurrent, metastatic or persistent cervical cancer remain extremely poor, there is an enormous need for novel immunotherapeutic approaches with curative potential such as ACT. Clinical trial C-145-04 (NCT03108495) is a prospective, phase II multicenter, open-label study evaluating the efficacy of a single autologous tumor infiltrating lymphocyte infusion (LN-145) followed by IL-2 after a non-myeloablative lymphodepletion (NMA-LD) regimen in patients with recurrent, metastatic, or persistent cervical cancer, who have failed at least one prior systemic therapy. The clinical trial requires resection of an adequate size tumor lesion, which is then shipped to a central GMP manufacturing facility for tumor infiltrating lymphocyte (TIL) extraction, expansion, and preparation of the final infusion product (LN-145). One week prior to LN-145 shipment and infusion, patients undergo NMA-LD consisting of cyclophosphamide (60 mg/kg) daily x 2 days followed by fludarabine (25 mg/m2) daily x 5 days. LN-145 is infused 24 hours after the last dose of fludarabine followed by up to 6 doses of IL-2 (600,000 IU/kg) every 8-12 hours. The primary endpoint is the ORR per RECIST v1.1. Secondary endpoints include complete response, duration of response, disease control rate, progression free- and overall survival and safety. Patients must, in addition to the tumor targeted for excision for TIL manufacture, have an additional measurable lesion for assessment of response. Other major eligibility criteria include: adequate bone marrow, liver, pulmonary, cardiac and renal function; ECOG performance status of 0 or 1. Systemic steroids greater than 10 mg/day prednisone equivalents are prohibited as are a history of serious immunotherapy-related adverse events. Citation Format: Amir Jazaeri, Robert Edwards, Robert Wenham, Koji Matsuo, Gini F. Fleming, David M. O9Malley, Brian Slomovitz, Bradley Monk, Robert J. Brown, Sam Suzuki, Igor Gorbatchevsky, Maria Fardis, Emese Zsiros. A phase 2 multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (LN-145) in patients with recurrent metastatic or persistent cervical carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT172.