450 Pooled analysis of efficacy outcomes from early-phase trials of tumor infiltrating lymphocyte therapy in advanced melanoma

<h3>Background</h3> Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) represents a promising strategy for the treatment of patients with advanced melanoma (MEL). In this study we performed a pooled analysis of efficacy outcomes of TIL in advanced MEL patients treated at Moffitt Cancer Center. <h3>Methods</h3> Data were extracted from 4 phase 1/2 clinical trials of MEL patients treated with TIL only, TIL with ipilimumab (ipi), TIL with nivolumab (nivo), and TIL with vemurafenib (vem). Progression-free survival (PFS) and overall-survival (OS) were assessed in both intention-to- treat [ITT] and TIL-treated [TT] patients. Clinical and TIL infusion product characteristics in relation to objective response rate (ORR) and PFS were analyzed in the TT population. <h3>Results</h3> From 2009–2018 60 MEL patients, 25 female (42%) and 35 male (58%), median age= 49 [IQR, 41–56], were enrolled in TIL only (n=19, 32%), TIL with ipi (n=13, 22%), TIL with nivo (n=11, 18%), and TIL with vem (n=17, 28%) trials. Ten (16.7%) patients did not receive TIL infusion after enrollment due to lack of TIL growth (n=2), adverse events (n=2), disease progression (n=5), and response to nivo (n=1). Among TT patients, 36 (72%) had elevated LDH, 17 (34%) liver, 9 (18%) brain metastases, and 12 (24%) received previous immune checkpoint blockade [ICB] therapy. Median numbers [IQR] of infused TIL and IL-2 dose were 59e⁹ [42-84e⁹] and 5 [4–6], respectively. Median follow up time was 102 months (95% CI 92–116). In ITT analyses, median PFS and OS were 7 (95% CI: 5–12) and 31 (95% CI: 21–88) months, respectively. In TT population, median PFS and OS were 10 (95% CI: 7–71) and 52 (95% CI: 24-not reached) months, respectively. ORR was 36% (18/50) with a complete response rate of 14% (7/50). LDH level, previous treatment, and received IL-2 doses were not associated with response. There was a trend towards lack of response in patients with liver metastases (p=0.05). The total number of infused TIL was associated with improved PFS (HR=0.26, 95% CI 0.11–0.59, p=0.003). Patients with objective response had a higher proportion of CD8⁺ cells in the infusion product (89% vs 54%, p=0.003) and higher post-treatment peak absolute lymphocyte count (6 vs 3 k/uL, p=0.03). Response to ICB therapy after ACT progression was 19% (4/21). <h3>Conclusions</h3> TIL therapy resulted in ORR of 36% and median OS of 52 months in patients with advanced MEL. Increased number of infused total TIL count and CD8⁺predominant TIL were associated with improved outcomes.