Abstract A003: Safety and efficacy of autologous tumor infiltrating lymphocyte therapy in pediatric and adolescent patients with immune checkpoint inhibitor-refractory metastatic melanoma: Results from a phase I clinical trial
Sameer Farouk Sait, Joshua Honeyman, Stacie Stapleton, Aaron Weiss, Ronald Zviti, Adam Greenbaum, Terri Seiders, Brian Gastman, Julia Glade Bender, Kevin CurranAbstract
Background:
Lifileucel is an autologous tumor infiltrating lymphocyte (TIL) therapy approved for adults with unresectable or metastatic melanoma previously treated with a PD-1 inhibitor and/or targeted therapy. Pediatric data have been lacking. We report preliminary safety, feasibility, and efficacy results from the melanoma cohort of a multicenter phase I study evaluating lifileucel in pediatric and adolescent patients (NCT06566092).
Methods:
Eligible patients underwent surgical resection of a metastatic lesion (≥1.5 cm) for ex vivo TIL generation. Manufacturing required approximately 4–6 weeks, during which bridging therapy was permitted. Treatment consisted of lymphodepletion (LD) with cyclophosphamide and fludarabine, a single infusion of lifileucel, and up to six doses of high-dose interleukin-2 (IL-2).
Results:
Five patients were enrolled across three centers. Median age at enrollment was 15 years (range, 14–17), and median follow-up was 7.5 months (range, 2–9). All patients had immune checkpoint inhibitor-refractory metastatic melanoma and had received multiple prior therapies: surgery (n=5), radiotherapy (n=3), immune checkpoint inhibitors (n=5), and targeted therapy (n=4). TIL manufacturing was successful in four patients. Three patients completed treatment. One patient experienced rapid disease progression and died prior to receiving therapy. Grade 3–4 treatment-related adverse events related to LD included cytopenias (n = 2), atrial thrombosis (n = 1), depressed level of consciousness (n = 1), hypocalcemia (n = 1), hypotension (n = 2), hypoxia (n = 1), fever (n = 2), urinary tract infection (n = 1), urine BK infection (n = 1). IL-2-related toxicities included capillary leak syndrome, hypervolemia, hypoxia and cytokine release syndrome which were manageable. No deaths related to LD or IL-2 were observed. One patient developed grade 2 uveitis considered related to TIL therapy. Among treated patients, two achieved confirmed partial responses (PR) per RECIST v1.1, while one experienced symptomatic improvement with resolution of malignant pleural effusions despite radiographic evidence of progressive disease (PD). One patient developed thrombotic microangiopathy with dialysis-dependent renal failure approximately 16 weeks after infusion and was treated with eculizumab, resulting in hematologic recovery but subsequently died (cause unknown) approximately 10 months after receiving TIL. At last follow-up after TIL therapy, two patients remained alive at 6 months (ongoing PR) and 9 months (PD).
Conclusions:
In the first reported pediatric/adolescent experience, lifileucel manufacturing and administration were feasible in adolescents with heavily pretreated metastatic melanoma. Early evidence of clinically meaningful antitumor activity was observed, including confirmed PRs in 2 of 3 treated patients. The safety profile was generally consistent with prior adult experience and supports long-term surveillance and multidisciplinary supportive care for delayed toxicities in this patient population.
Citation Format:
Sameer Farouk Sait, Joshua Honeyman, Stacie Stapleton, Aaron Weiss, Ronald Zviti, Adam Greenbaum, Terri Seiders, Brian Gastman, Julia Glade Bender, Kevin Curran. Safety and efficacy of autologous tumor infiltrating lymphocyte therapy in pediatric and adolescent patients with immune checkpoint inhibitor-refractory metastatic melanoma: Results from a phase I clinical trial [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Bridging Discovery and Clinical Impact in Pediatric Cancer; 2026 Sep 22-25; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_1):Abstract nr A003.