Abstract P050: Trial in progress: A phase 2 multicenter study of autologous tumor-infiltrating lymphocyte (TIL, LN-145) cell therapy in patients with metastatic non-small cell lung cancer (mNSCLC)

Abstract

Abstract 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 patients with mNSCLC 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 CR. This provides a clear rationale for initiation of IOV-LUN-202 study, evaluating 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. Cohorts 1 and 2 (each, n=40) are enrolling patients with mNSCLC based on tumor proportion score (TPS; Cohort 1, TPS <1%; Cohort 2, TPS ≥1%) at metastatic diagnosis prior to ICI use. Cohort 3 (TPS <1%; n=15) uses core biopsies for tumor acquisition in patients unable to undergo a surgical harvest, and Cohort 4 is designated for patients requiring retreatment. LN-145 is a cryopreserved infusion product generated at centralized GMP facilities in a 22 day manufacturing process. All patients receive TIL therapy consisting of nonmyeloablative lymphodepletion with cyclophosphamide (60 mg/kg × 2) + fludarabine (25 mg/m2 × 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 criteria include age ≥ 18 y, 1 prior line of therapy, ≥1 lesion(s) available for TIL generation and a remaining RECIST-measurable lesion, and ECOG PS 0–1. For each cohort the primary endpoint is ORR per RECIST 1.1. Secondary endpoints are safety, complete response rate, duration of response, disease control rate, progression-free survival, overall survival, and efficiency of generating LN-145 from tumor core biopsies (Cohort 3). Citation Format: Erminia Massarelli, Selda Samakoglu, Viktoria Gontcharova, Guang Chen, Madan Jagasia, Friedrich Graf Finckenstein, Ammar Sukari. Trial in progress: A phase 2 multicenter study of autologous tumor-infiltrating lymphocyte (TIL, LN-145) cell therapy in patients with metastatic non-small cell lung cancer (mNSCLC) [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2021 Oct 7-10. Philadelphia (PA): AACR; Mol Cancer Ther 2021;20(12 Suppl):Abstract nr P050.