A Phase Ii Study To Assess The Efficacy And Safety Of Autologous Tumor Infiltrating Lymphocytes (Ln-145) Alone And In Combination With Anti-Pd-L1 Inhibitor Durvalumab (Medi4736) In Patients With Locally Advanced Or Metastatic Non-Small Cell Lung Cancer (Nsclc)

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has demonstrated efficacy in the treatment of immunogenic tumors with high mutational burden such as melanoma. Durable complete response rate was reported at 24% in metastatic melanoma suggesting a strong role for treatment with one time therapy of TIL in such disease. NSCLC possesses a high mutation burden, and the presence of TIL in these tumors have been correlated with improved outcomes. Durvalumab, an inhibitor of PD-L1, together with other checkpoint inhibitors are approved therapies for NSCLC. However, there remains significant need to improve outcomes in these patients. Since checkpoint blockade augments natural anti-tumor immunity, the co-administration of the anti-PD-L1 inhibitor antibody, durvalumab, with TIL therapy may improve outcomes in patients naive to anti-PD-1 or anti-PD-L1NSCLC. IOV-LUN-201 is a phase II multicenter, open-label study designed to evaluate the efficacy and safety of autologous TIL (LN-145) therapy alone (Cohort 1) or in combination with durvalumab (Cohort 2), for the treatment of patients with locally-advanced or metastatic (Stage III or IV) NSCLC who have received ≥ 1 line of prior systemic therapy but who have not received prior immune checkpoint inhibitors. LN-145 is prepared in 22 days at a central GMP facility from lymphocytes extracted from a surgically-resected sample of patient tumor. LN-145 infusion is preceded by a non-myeloablative lymphodepletion regimen of cyclophosphamide and fludarabine. LN-145 infusion is then followed by IL-2 at 600,000 IU/kg for up to 6 doses. Cohort 1 patients will receive the standard LN-145 regimen including lymphodepletion and subsequent IL-2. Patients who progress after receiving LN-145, or who do not receive LN-145 may go on to receive single-agent durvalumab. Cohort 2 patients receive an initial dose of durvalumab 2 weeks prior to tumor resection followed by a second dose 2 weeks following resection prior to LN-145 infusion. Durvalumab therapy resumes 2 weeks following LN-145 infusion. All patients in Cohort 2, including those unable to receive LN-145, will resume durvalumab therapy Q4W until disease progression or unacceptable toxicity. A minimum of 2 tumor lesions are required: 1 for resection/TIL manufacture and 1 for assessment of response by RECIST 1.1. Other major eligibility criteria include adequate bone marrow/cardiac/liver/pulmonary/renal function and ECOG PS of 0 or 1. Efficacy will be assessed as a function of ORR, CR rate, DOR, DCR, and PFS per RECIST 1.1 and OS. Assessment of safety data will be descriptive and based on the summarization of TEAEs, SAEs, AEs leading to discontinuation from treatment/study, vital signs, physical examinations and clinical laboratory tests. Citation Format: Sylvia Lee, Viktoriya Villaflor, Missack Haigentz, Kumar Karyampudi, Susie Tanamly, Sam Suzuki, Igor Gorbatchevsky, Maria Fardis, Liza Villaruz. A phase II study to assess the efficacy and safety of autologous tumor infiltrating lymphocytes (LN-145) alone and in combination with anti-PD-L1 inhibitor durvalumab (MEDI4736) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) [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 CT173.