{"entity":{"id":"paper-c-144-01-lifileucel-melanoma-jco-2021","kind":"paper","name":"C-144-01: lifileucel, tumour-infiltrating lymphocytes grown from a patient's own tumour, in melanoma after checkpoint inhibitors have failed","aka":[],"tldr":"Immune cells harvested from a patient's tumour, expanded in the lab and reinfused shrank melanoma in 36% of patients whose disease had progressed on PD-1 blockade, with responses that mostly lasted.","summary":"Cohort 2 of the C-144-01 phase 2 trial treated 66 patients with advanced melanoma that had progressed after anti-PD-1 therapy (and BRAF/MEK inhibitors where indicated; median 3.3 prior lines) with a single infusion of lifileucel, autologous tumour-infiltrating lymphocytes expanded centrally over about 22 days, after non-myeloablative lymphodepletion and followed by up to six doses of high-dose interleukin-2. The objective response rate was 36% (2 complete, 22 partial) with disease control in 80%; median duration of response was not reached at 18.7 months of follow-up. Adverse events were largely attributable to lymphodepletion and IL-2 and resolved within two weeks, with two treatment-related deaths. Pooled analysis of 153 patients from cohorts 2 and 4 showed a 31% response rate and supported FDA accelerated approval in February 2024, the first TIL therapy and first cell therapy for a solid tumour.","asOf":"2026-09-08","links":[{"label":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=C-144-01%20lifileucel%20tumor-infiltrating%20lymphocyte%20melanoma%20Sarnaik%20JCO%202021"},{"label":"ClinicalTrials.gov NCT02360579","url":"https://clinicaltrials.gov/study/NCT02360579"}],"tags":[],"related":["paper-rohaas-til-vs-ipilimumab-nejm-2022"],"cancers":["melanoma"],"sections":[],"technologies":["til-therapy"],"targets":[],"drugs":["lifileucel","aldesleukin","cyclophosphamide"],"companies":["iovance"],"institutions":["moffitt","nci"],"pathways":[],"terms":["tils","orr"],"trials":["c-144-01"],"people":["amod-sarnaik","steven-rosenberg"],"bottlenecks":["b-manufacturing-cell-therapy","b-immunotherapy-response"],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2021,"doi":"10.1200/JCO.21.00612","pmid":"33979178","authors":"Sarnaik AA, Hamid O, Khushalani NI, et al.","paperType":"translational","findings":["66 patients with anti-PD-1-refractory advanced melanoma; median 3.3 prior therapies; single lifileucel infusion after cyclophosphamide-fludarabine lymphodepletion, then up to 6 doses of high-dose IL-2.","Objective response 36% (3% complete); disease control 80%.","Median duration of response not reached at 18.7 months; responses deepened over time in some patients.","Grade 3-4 adverse events mostly cytopenias, febrile neutropenia and IL-2-related hypotension, resolving within 2 weeks; 2 treatment-related deaths.","Pooled cohorts 2 and 4 (153 patients): objective response 31.4%, supporting accelerated approval in 2024."],"whatItMeans":"Lifileucel proved that Steven Rosenberg's decades-old TIL concept could be industrialised into a licensed product and gave patients with checkpoint-refractory melanoma, who otherwise have few options, a chance of durable remission. It is the first cell therapy approved for any solid tumour. The treatment requires surgery to harvest tumour, hospitalisation for lymphodepletion and IL-2, and specialised centres, so its reach is limited.","caveats":["Single-arm trial; approval rested on response rate rather than survival.","Toxic conditioning and high-dose IL-2 make the regimen unsuitable for frail patients.","Manufacturing takes about three weeks and needs a resectable lesion; not all patients yield a product.","Cost (list price above 500,000 US dollars) and centre requirements restrict access."],"changedPractice":true,"participants":66},"route":"/key-papers/paper-c-144-01-lifileucel-melanoma-jco-2021/","neighbours":{"paper":[{"id":"paper-rohaas-til-vs-ipilimumab-nejm-2022","kind":"paper","name":"Rohaas 2022: the first randomised trial of TIL therapy, against ipilimumab, in advanced melanoma","route":"/key-papers/paper-rohaas-til-vs-ipilimumab-nejm-2022/"},{"id":"paper-spearhead-1-lancet-2024","kind":"paper","name":"SPEARHEAD-1: afamitresgene autoleucel, the first engineered T-cell receptor therapy approved for a solid tumour, in synovial sarcoma","route":"/key-papers/paper-spearhead-1-lancet-2024/"}],"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"technology":[{"id":"til-therapy","kind":"technology","name":"TIL therapy","route":"/technologies/til-therapy/"}],"drug":[{"id":"aldesleukin","kind":"drug","name":"Aldesleukin (high-dose IL-2)","route":"/drugs/aldesleukin/"},{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"lifileucel","kind":"drug","name":"Lifileucel","route":"/drugs/lifileucel/"}],"company":[{"id":"iovance","kind":"company","name":"Iovance Biotherapeutics","route":"/companies/iovance/"}],"institution":[{"id":"moffitt","kind":"institution","name":"Moffitt Cancer Center","route":"/institutions/moffitt/"},{"id":"nci","kind":"institution","name":"National Cancer Institute (NIH)","route":"/institutions/nci/"}],"term":[{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"},{"id":"tils","kind":"term","name":"Tumour-infiltrating lymphocytes (TILs)","route":"/terms/tils/"}],"trial":[{"id":"c-144-01","kind":"trial","name":"C-144-01","route":"/trials/c-144-01/"}],"person":[{"id":"amod-sarnaik","kind":"person","name":"Amod A. Sarnaik","route":"/people/amod-sarnaik/"},{"id":"steven-rosenberg","kind":"person","name":"Steven A. Rosenberg","route":"/people/steven-rosenberg/"}],"bottleneck":[{"id":"b-manufacturing-cell-therapy","kind":"bottleneck","name":"Manufacturing cost and time for living and radioactive medicines","route":"/bottlenecks/b-manufacturing-cell-therapy/"},{"id":"b-immunotherapy-response","kind":"bottleneck","name":"No one can predict who responds to immunotherapy","route":"/bottlenecks/b-immunotherapy-response/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}