Abstract CT235: A Phase 2, multicenter study of autologous tumor infiltrating lymphocytes (TIL, LN 144/LN-145/LN-145-S1) in patients with solid tumors
Authors: Gettinger Scott , Kluger Harriet , Schoenfeld Adam , Betof-Warner Allison , He Kai , Sukari Ammar , Doger de Speville Uribe Bernard , Lee Sylvia , Haefliger Simon , Goldberg Zelanna , Cacovean Alex , Fiaz Rana , Chen Guang , Jagasia Madan , Finckenstein Friedrich Graf , Fardis Maria , Jimeno Antonio 
Published: July 2021

Background TIL (especially CD8+ T cells) in the tumor microenvironment is associated with survival outcomes in many solid tumors, including melanoma (Mel), head and neck squamous cell carcinoma (HNSCC), and non-small cell lung cancer (NSCLC). Lifileucel (LN-144), has shown efficacy with durable responses in advanced melanoma (Mel) (Sarnaik et al., ASCO 2020), metastatic cervical cancer (Jazaeri et al., ASCO 2019), and LN-145 + pembrolizumab in HNSCC (Jimeno et al., SITC 2020). TIL therapy has shown evidence of efficacy in metastatic NSCLC in a Phase 1 study (Creelan et al., ASCO 2020). Methods IOV-COM-202 (NCT03645928) is a Phase 2 global, open-label multi-cohort, non-randomized study designed to evaluate the safety and efficacy of TIL therapy as a single agent or in combination with immune checkpoint inhibitors. All patients receive either, lifileucel, LN-145 or LN-145-S1 (PD-1 select TIL), which is manufactured at centralized GMP facilities generating a cryopreserved infusion product which is shipped to the treatment centers. Cohort 1, 2 and 3 enroll Mel, HNSCC and NSCLC patients, respectively (Table 1). Patients undergo a nonmyeloablative lymphodepletion (NMA-LD) regimen prior to TIL infusion, followed by up to 6 doses of intravenous IL-2. Patients in Cohorts 1A, 2A, and 3A start pembrolizumab following tumor harvest for TIL generation, but prior to NMA-LD. Pembrolizumab is dosed per label. Patients in Cohorts 1B, IC and 3B receive LN-145-S1, lifileucel, and LN-145, respectively. Cohort 3C patients receive a dose of ipilimumab and nivolumab prior to tumor harvest, with nivolumab continuing Q4W for up to 2 years, or until progression or unacceptable toxicity. Key eligibility includes: ≥ 18 years of age; RECIST measurable disease; ≥ 1 lesion(s) available for TIL generation; ECOG PS 0-1. The primary endpoint: ORR per RECIST v1.1. Secondary endpoints: safety, CR rate, DOR, DCR, PFS, and OS.

Table 1.IOV-COM-202 Study DesignCohortTIL ManufacturingCohort 1A: Melanoma PD-1/ PD-L1 Naïve LN-144 + Pembrolizumab N=12LN-144: 22-day manufacturingCohort 1B: Melanoma ≥1 prior systemic therapies LN-145-S1 N up to 27LN-145-S1: PD-1 selected TILCohort 1C: Melanoma ≥1 prior systemic therapies LN-144 Gen 3 N up to 27LN-144 Gen 3: 16-day manufacturingCohort 2A: Head and Neck PD-1/ PD-L1 Naïve LN-145 + Pembrolizumab N=19LN-145: 22-day manufacturingCohort 3A: NSCLC PD-1/ PD-L1 Naïve LN-145 + Pembrolizumab N=12LN-145: 22-day manufacturingCohort 3B: NSCLC ≥1 prior systemic therapies LN-145 N=12LN-145: 22-day manufacturingCohort 3C: NSCLC 1 prior systemic therapy TIL + Ipilimumab / Nivolumab N up to 26

Citation Format: Scott Gettinger, Harriet Kluger, Adam Schoenfeld, Allison Betof-Warner, Kai He, Ammar Sukari, Bernard Doger de Speville Uribe, Sylvia Lee, Simon Haefliger, Zelanna Goldberg, Alex Cacovean, Rana Fiaz, Guang Chen, Madan Jagasia, Friedrich Graf Finckenstein, Maria Fardis, Antonio Jimeno. A Phase 2, multicenter study of autologous tumor infiltrating lymphocytes (TIL, LN 144/LN-145/LN-145-S1) in patients with solid tumors [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 CT235.