Safety and efficacy of adoptive cell transfer using autologous tumor infiltrating lymphocytes (LN-145) for treatment of recurrent, metastatic, or persistent cervical carcinoma.

2538 Background: There is a high unmet medical need for effective treatments for patients with recurrent, metastatic, or persistent cervical cancer. Most patients are young and survival rates are poor. ORR for second line therapies is between 4 and 14% for chemotherapy and recently approved immunotherapy. Adoptive cell transfer using tumor infiltrating lymphocytes (TIL) have demonstrated durable responses in some patients with recurrent cervical cancer thus offering the potential for long-term disease control. Methods: Study C-145-04 is an ongoing, open-label, multicenter Phase 2 clinical trial evaluating the safety and efficacy of LN-145 TIL therapy in patients with advanced cervical cancer who have undergone at least one prior line of chemotherapy. Prior checkpoint inhibitor therapy is an exclusion criterion. The primary endpoint is ORR per RECIST 1.1; secondary endpoints include duration of response (DOR), disease control rate (DCR), and LN-145 safety. Tumors surgically harvested at local institutions are shipped to central GMP facilities for TIL generation in a 22-day manufacturing process. Final LN-145 TIL product is cryopreserved and shipped to sites. Patients receive one week of preconditioning lymphodepletion (cyclophosphamide, fludarabine), a single LN-145 infusion, followed by up to 6 doses of IL-2 (600,000 IU/kg). Results: As of 4 Feb 2019, 27 efficacy-c patients have received Gen 2 of LN-145, with a mean age of 47 years and 2.6 mean prior lines of therapy. Preliminary efficacy results: ORR was 44% (1 CR, 9 PR, 2 uPR), DCR was 89% at 3.5-month median study follow-up with 11/12 patients maintaining their response. Improved responses were observed in 4 patients with longer follow-up. Mean TIL cells infused was 28x10 9 . Median IL-2 doses administered was 6.0. The adverse event profile was generally consistent with the underlying advanced disease and the profile of the lymphodepletion and IL-2 regimens. Conclusions: LN-145 results in 44% ORR in previously treated cervical cancer patients with acceptable safety and efficacy profile. LN-145 offers patients a viable therapeutic option warranting further investigation. Clinical trial information: NCT03108495.