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Background Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has shown promising efficacy in melanoma, however limited response has been seen in other solid tumor types. In this study, we assess the efficacy of ACT with TIL in combination with lymphodepletion and IL-2. The primary objective was to determine the objective response rate (ORR) of TIL therapy across multiple solid tumor types. Secondary objectives included assessment of survival and disease control rate (DCR), as well as characterization of safety.Methods This was a phase II, non-comparative study ( NCT03449108). All patients underwent excisional biopsy followed by ex vivo TIL generation. After successful TIL production, lymphodepletion with cyclophosphamide (60mg/kg/day IV on days -7 and -6) and fludarabine (25mg/m2 IV on days -5 through -1) was initiated. TIL infusion occurred on study day 0 and was followed by up to 6 doses of IL-2 (600,000 IU/kg). During the study, the protocol was amended to utilize a PD-1-selected TIL product and to include priming dual immune-checkpoint inhibition for all cohorts except anaplastic thyroid to increase early T cell activation.Results The trial enrolled 30 patients who underwent tissue harvest. Of this cohort, 3 had insufficient TIL growth (less than 250 x 10 6 viable TIL), 4 experienced rapid progression and decline in performance status, 1 developed new lab abnormalities, and 1 received TIL without IL-2. Thus, 21 patients were ultimately evaluable for the primary efficacy endpoint and primary safety analysis. There were 7 patients with ovarian cancer, 13 with bone or soft tissue sarcoma, and 1 with anaplastic thyroid cancer. The median number of IL-2 doses was 4 (range 1-6). There were no DLTs. Grade 3 treatment-related adverse events (TRAEs) occurred in 81.0% (17/21) of patients. Grade 4 TRAEs occurred in 76.2% (16/21) of patients, of which all but three events related to myelosuppression. In terms of response, 16 patients achieved a best response of at least SD resulting in a DCR of 76.2% (95% CI 52.8-91.8%, figure 1). The ORR was 0% with no confirmed responses. The median PFS was 2.73 months (95% CI 2.40-2.83, figure 2). The median OS was 9.53 months (95% CI 6.77-19.7, figure 2).Conclusions TIL therapy was safe and overall well-tolerated, however did not demonstrate clinical efficacy in the tested indications. Additional modifications to the TIL treatment regimen will be required in future studies, such as genetic manipulation of TIL and alternative doses of lymphodepletion and cytokines post TIL infusion.Trial Registration NCT03449108Ethics Approval Ethics approval was obtained by the MD Anderson IRB under protocol 2017-0672.Consent No sensitive information is included in this abstract. All patient information has been de-identified.Abstract 1338 Figure 1Spider plot demonstrating percentage change in size of target lesions from baseline over time per RECIST v1.1Abstract 1338 Figure 2Kaplan-Meier progression-free (A) and overall (B) survival for entire cohort