Use of lenvatinib as bridging therapy for patients undergoing treatment with lifileucel: a single institution experience

Background: Lifileucel, a one-time autologous tumor-infiltrating lymphocyte cell therapy, is approved for advanced (unresectable or metastatic) melanoma previously treated with a PD-1-blocking antibody, and, if BRAF V600 mutation-positive, a BRAF inhibitor with or without a MEK inhibitor.Cohort 1A of the IOV-COM-202 study (NCT03645928) assesses the efficacy and safety of lifileucel and pembrolizumab in an earlier setting for patients with immune checkpoint inhibitor (ICI)-naive advanced melanoma.Methods: Eligible patients may have received a BRAF/MEK inhibitor if BRAF mutation-positive.Patients must have 1 resectable lesion (1.5 cm diameter) for 22-day cryopreserved lifileucel manufacturing, and 1 measurable lesion for response assessment (RECIST v1.1).Treatment regimen consists of pembrolizumab, nonmyeloablative lymphodepletion (cyclophosphamide and fludarabine), a single lifileucel infusion (110 9 -15010 9 cells), followed by up to 6 doses of IL-2 (600,000 IU/kg IV), and continued pembrolizumab until disease progression, unacceptable toxicity, or up to 24 months.Primary endpoints were ORR and incidence of grade 3 TEAEs.Results: As of 17 Apr 2024, 23 patients with a median (range) age of 51.0 (18-68) years received treatment.At baseline, median (range) target lesion sum of diameters was 50.0 (14-355) mm.At study entry, 14 patients (60.9%) had visceral metastases (M1b-M1d), 8 (34.8%) had BRAF V600 mutations, and 3 (13.0%)had prior BRAF/MEK inhibitor treatment.Confirmed ORR was 65.2% (15/23), including 30.4% (7/23) CR, 34.8% (8/23) PR, and 26.1% (6/23) SD.Median time to initial response was 2.6 months.All evaluable patients had regression of target lesions; responses deepened over time.At a median follow-up of 21.7 months, median duration of response was not reached; 10/15 (66.7%) patients had ongoing response and 3 patients (20%) discontinued study while in response.TEAEs were consistent with the underlying disease and known manageable safety profiles of single administration of lifileucel and continued pembrolizumab.Late AEs were consistent with anti-PD-1 monotherapy and were differentiated from ICI combination therapies.Conclusions: These results support further evaluation of lifileucel and pembrolizumab as frontline treatment for advanced melanoma in the phase 3 TILVANCE-301 study (NCT05727904).