dc.contributor.author | Chesney, J | |
dc.contributor.author | Lewis, KD | |
dc.contributor.author | Kluger, H | |
dc.contributor.author | Hamid, O | |
dc.contributor.author | Whitman, E | |
dc.contributor.author | Thomas, S | |
dc.contributor.author | Wermke, M | |
dc.contributor.author | Cusnir, M | |
dc.contributor.author | Domingo-Musibay, E | |
dc.contributor.author | Phan, GQ | |
dc.contributor.author | Kirkwood, JM | |
dc.contributor.author | Hassel, JC | |
dc.contributor.author | Orloff, M | |
dc.contributor.author | Larkin, J | |
dc.contributor.author | Weber, J | |
dc.contributor.author | Furness, AJS | |
dc.contributor.author | Khushalani, NI | |
dc.contributor.author | Medina, T | |
dc.contributor.author | Egger, ME | |
dc.contributor.author | Graf Finckenstein, F | |
dc.contributor.author | Jagasia, M | |
dc.contributor.author | Hari, P | |
dc.contributor.author | Sulur, G | |
dc.contributor.author | Shi, W | |
dc.contributor.author | Wu, X | |
dc.contributor.author | Sarnaik, A | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2023-03-22T13:52:29Z | |
dc.date.available | 2023-03-22T13:52:29Z | |
dc.date.issued | 2022-12-01 | |
dc.identifier | ARTN e005755 | |
dc.identifier | jitc-2022-005755 | |
dc.identifier.citation | Journal for ImmunoTherapy of Cancer, 2022, 10 (12), pp. e005755 - | en_US |
dc.identifier.issn | 2051-1426 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/5725 | |
dc.identifier.eissn | 2051-1426 | |
dc.identifier.eissn | 2051-1426 | |
dc.identifier.doi | 10.1136/jitc-2022-005755 | |
dc.description.abstract | BACKGROUND: Patients with advanced melanoma have limited treatment options after progression on immune checkpoint inhibitors (ICI). Lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, demonstrated an investigator-assessed objective response rate (ORR) of 36% in 66 patients who progressed after ICI and targeted therapy. Herein, we report independent review committee (IRC)-assessed outcomes of 153 patients treated with lifileucel in a large multicenter Phase 2 cell therapy trial in melanoma. METHODS: Eligible patients had advanced melanoma that progressed after ICI and targeted therapy, where appropriate. Melanoma lesions were resected (resected tumor diameter ≥1.5 cm) and shipped to a central good manufacturing practice facility for 22-day lifileucel manufacturing. Patients received a non-myeloablative lymphodepletion regimen, a single lifileucel infusion, and up to six doses of high-dose interleukin-2. The primary endpoint was IRC-assessed ORR (Response Evaluation Criteria in Solid Tumors V.1.1). RESULTS: The Full Analysis Set consisted of 153 patients treated with lifileucel, including longer-term follow-up on the 66 patients previously reported. Patients had received a median of 3.0 lines of prior therapy (81.7% received both anti-programmed cell death protein 1 and anti-cytotoxic lymphocyte-associated protein 4) and had high disease burden at baseline (median target lesion sum of diameters (SOD): 97.8 mm; lactate dehydrogenase (LDH) >upper limit of normal: 54.2%). ORR was 31.4% (95% CI: 24.1% to 39.4%), with 8 complete responses and 40 partial responses. Median duration of response was not reached at a median study follow-up of 27.6 months, with 41.7% of the responses maintained for ≥18 months. Median overall survival and progression-free survival were 13.9 and 4.1 months, respectively. Multivariable analyses adjusted for Eastern Cooperative Oncology Group performance status demonstrated that elevated LDH and target lesion SOD >median were independently correlated with ORR (p=0.008); patients with normal LDH and SOD <median had greater likelihood of response than those with either (OR=2.08) or both (OR=4.42) risk factors. The most common grade 3/4 treatment-emergent adverse events (≥30%) were thrombocytopenia (76.9%), anemia (50.0%), and febrile neutropenia (41.7%). CONCLUSIONS: Investigational lifileucel demonstrated clinically meaningful activity in heavily pretreated patients with advanced melanoma and high tumor burden. Durable responses and a favorable safety profile support the potential benefit of one-time lifileucel TIL cell therapy in patients with limited treatment options in ICI-refractory disease. | |
dc.format | Print | |
dc.format.extent | e005755 - | |
dc.language | eng | |
dc.language.iso | eng | en_US |
dc.publisher | BMJ PUBLISHING GROUP | en_US |
dc.relation.ispartof | Journal for ImmunoTherapy of Cancer | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0 | en_US |
dc.subject | Clinical Trials, Phase II as Topic | |
dc.subject | Immunotherapy | |
dc.subject | Immunotherapy, Adoptive | |
dc.subject | Lymphocytes, Tumor-Infiltrating | |
dc.subject | Melanoma | |
dc.subject | Humans | |
dc.subject | Immune Checkpoint Inhibitors | |
dc.subject | Immunotherapy, Adoptive | |
dc.subject | Lymphocytes, Tumor-Infiltrating | |
dc.subject | Melanoma | |
dc.subject | Skin Neoplasms | |
dc.title | Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapies: pooled analysis of consecutive cohorts of the C-144-01 study. | en_US |
dc.type | Journal Article | |
dcterms.dateAccepted | 2022-11-09 | |
dc.date.updated | 2023-03-22T13:51:20Z | |
rioxxterms.version | VoR | en_US |
rioxxterms.versionofrecord | 10.1136/jitc-2022-005755 | en_US |
rioxxterms.licenseref.startdate | 2022-12-01 | |
rioxxterms.type | Journal Article/Review | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/36600653 | |
pubs.issue | 12 | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.organisational-group | /ICR/ImmNet | |
pubs.publication-status | Published | |
pubs.publisher-url | http://dx.doi.org/10.1136/jitc-2022-005755 | |
pubs.volume | 10 | |
icr.researchteam | Skin Unit | en_US |
dc.contributor.icrauthor | Furness, Andrew | |
icr.provenance | Deposited by Mr Arek Surman on 2023-03-22. Deposit type is initial. No. of files: 1. Files: Efficacy and safety of lifileucel, a one-time autologous tumor-infiltrating lymphocyte (TIL) cell therapy, in patients with .pdf | |