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: 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
Journal: Cancer Research (2021)

Abstract 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.