Abstract CT130: Trial in progress: A phase 2 multicenter study (IOV-LUN-202) of autologous tumor-infiltrating lymphocyte (TIL) cell therapy (LN-145) in patients with metastatic non-small cell lung cancer (mNSCLC) (2022)

Abstract Background: Patients with mNSCLC without actionable driver mutations have limited second-line (2L) options after progression on concurrent or sequential front-line immune checkpoint inhibitors (ICI) and platinum-based chemotherapy ± bevacizumab. Early clinical experience with LN-145, an autologous TIL cell therapy, in heavily pretreated patients with mNSCLC has demonstrated feasibility, safety, and a 21.4% objective response rate (ORR), including 2 of 6 responders with PD-L1-negative tumors (Schoenfeld AJ, SITC 2021 [abs 458]). Based on the results of this signal-finding study and to address an unmet medical need in 2L, we amended the ongoing IOV-LUN-202 study, evaluating LN-145 in patients with stage IV mNSCLC after confirmed disease progression on front-line standard-of-care treatment, including concurrent or sequential ICI + chemotherapy ± bevacizumab. Methods: IOV-LUN-202 (NCT04614103) is an open-label, nonrandomized, phase 2 study. Cohorts 1 (tumor proportion score [TPS] &amp;lt;1% prior to ICI use or no historical TPS) and 2 (TPS ≥1% prior to ICI use) are actively enrolling patients. Cohort 3 (any TPS) uses core biopsies for tumor procurement and a 16-day Gen 3 manufacturing process for patients unable to undergo surgical resection. A retreatment cohort (n not prespecified) will enroll prior responders to LN-145 or patients with unconfirmed progressive disease from cohorts 1-3. A total of approximately 95 patients is planned for cohorts 1-3. Key eligibility criteria include mNSCLC with no EGFR, ALK, or ROS1 genomic alterations, progressing after ≤2 prior lines of therapy (if concurrent ICI + chemotherapy; ≤3 prior lines if sequential), including targeted therapy in those with actionable mutations (eg, MET, HER2, RET, BRAF, KRAS); in those without actionable mutations, progression after 1 prior concurrent ICI + chemotherapy (≤2 prior lines if sequential); ≥1.5-cm lesion(s) for TIL generation; ≥1 remaining RECIST-measurable lesion(s) after tumor harvest; and ECOG PS of 0 or 1. Tumor harvest and TIL manufacturing can occur before or after confirmed progression. LN-145 is generated at centralized GMP facilities, and the final cryopreserved infusion product is shipped to the sites. Upon progression, patients receive a conditioning regimen of nonmyeloablative lymphodepletion with 2 doses of cyclophosphamide (60 mg/kg) and 5 doses of fludarabine (25 mg/m2), followed by one-time infusion of LN-145 (1-150 × 109 cells), and ≤6 doses of IL-2 (600,000 IU/kg). The primary endpoint is ORR per RECIST v1.1. Secondary endpoints include complete response rate, duration of response, disease control rate, progression-free survival, overall survival, and safety (incidence of Grade ≥3 treatment-emergent adverse events [AEs] and serious AEs). Citation Format: Jason Alan Chesney, Adam J. Schoenfeld, Trisha Wise-Draper, Ammar Sukari, Kai He, Friedrich Graf Finckenstein, Parameswaran Hari, Madan Jagasia, Selda Samakoglu, Ann Leighton-Swayze, Guang Chen, Yong Ki Hong. Trial in progress: A phase 2 multicenter study (IOV-LUN-202) of autologous tumor-infiltrating lymphocyte (TIL) cell therapy (LN-145) in patients with metastatic non-small cell lung cancer (mNSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT130.