Abstract CT246: A phase 2 multicenter study of autologous tumor infiltrating lymphocytes (TIL, LN-145) cell therapy in patients with metastatic non-small cell lung cancer (mNSCLC)
Authors: Massarelli Erminia , Goldberg Zelanna , Cacovean Alex , Yadav Bhagyashree , Chen Guang , Jagasia Madan , Finckenstein Friedrich Graf , Fardis Maria , Sukari Ammar 
Published: July 2021

Abstract
Background Patients with mNSCLC without actionable driver mutation(s) who have progressed after cytotoxic chemotherapy plus immune checkpoint inhibitors (ICI) ± bevacizumab have limited treatment options and represent an unmet need. The safety and efficacy of TIL cell therapy for mNSCLC patients who failed to respond or progressed on nivolumab has been evaluated in a Phase 1 clinical trial (Creelan B., AACR 2020), demonstrating an objective response rate (ORR) of 25% including 17% durable CRs. This provides a clear rationale for initiation of IOV-LUN-202 study, evaluating Iovance Gen 2 TIL cell therapy with LN-145 in patients with mNSCLC without actionable driver mutation(s), who have progressed on or following a single line of approved systemic therapy consisting of combined ICI + chemotherapy ± bevacizumab.
Trial Design IOV-LUN-202 (NCT04614103) is a prospective, open-label, multi-cohort, non-randomized, multicenter Phase 2 study. Patient cohorts (n=40 ea) based on tumor proportion score (TPS) at metastatic diagnosis prior to ICI use are Cohort 1 (TPS &lt;1%) and Cohort 2 (TPS ≥ 1%). Cohort 3 (TPS &lt;1%; n=15), utilizes core biopsies for tumor acquisition for patients unable to undergo a surgical harvest. LN-145 is generated at centralized GMP facilities and the final cryopreserved infusion product is shipped to the sites. All patients receive TIL therapy consisting of nonmyeloablative lymphodepletion with cyclophosphamide (60 mg/kg X 2) + fludarabine (25 mg/m2 X 5), followed by a single infusion of autologous LN-145 (Day 0) and up to 6 doses of IL-2 (600,000 IU/kg). Key eligibility includes: ≥ 18 y of age; 1 prior line of therapy; ≥ 1 lesion(s) available for TIL generation and a remaining RECIST-measurable lesion; and ECOG PS of 0-1. For each cohort, the primary endpoint is ORR per RECIST 1.1. Secondary endpoints are safety, CR rate, DOR, DCR, PFS, OS and efficiency of generating LN-145 from tumor core biopsies (Cohort 3).
Table 1.IOV-LUN-202 Patient CohortsPATIENT POPULATIONCOHORTMetastatic NSCLC without an actionable driver mutation and progressive disease on or following a single line of approved systemic therapy including ICI + Chemo ± BevacizumabSAMPLE SIZE1PD-L1 TPS &lt; 1%N = 402PD-L1 TPS ≥ 1%N = 403PD-L1 TPS &lt; 1%/Core BiopsiesN = 154RetreatmentN = undefined
Citation Format: Erminia Massarelli, Zelanna Goldberg, Alex Cacovean, Bhagyashree Yadav, Guang Chen, Madan Jagasia, Friedrich Graf Finckenstein, Maria Fardis, Ammar Sukari. A phase 2 multicenter study of autologous tumor infiltrating lymphocytes (TIL, LN-145) cell therapy in patients with metastatic non-small cell lung cancer (mNSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT246.