Lifileucel inotenderwa neUSFDA kune isina kugadzirwa kana metastatic melanoma

Iyo Food and Drug Administration yakapa mvumo yakakurumidza ku lifileucel (Amtagvi, Iovance Biotherapeutics, Inc.) musi waKukadzi 16, 2024. Mvumo iyi ndeyevarwere vakuru vane unresectable kana metastatic melanoma vakamborapwa nePD-1 inovhara masoja ekudzivirira chirwere. Pamusoro pezvo, varwere vanofanirwa kunge vari BRAF V600 yakanaka uye vakagamuchira BRAF inhibitor ine kana isina MEK inhibitor.

An open-label, single-arm trial was conducted globally across multiple centers and cohorts to assess the safety and effectiveness in patients with unresectable or metastatic melanoma. These patients had received prior treatment with at least one systemic therapy, which included a PD-1 blocking antibody. If they tested positive for the BRAF V600 mutation, they had also been treated with a BRAF inhibitor, with or without a MEK inhibitor. Out of 89 patients who were given lifileucel, two were omitted because the product did not fulfill specifications and five were excluded owing to product comparability. Lifileucel was given after a lymphodepleting treatment regimen which included cyclophosphamide at a dose of 60 mg/kg daily with mesna for 2 days, followed by fludarabine at a dose of 25 mg/m2 daily for 5 days. Patients were administered IL-2 (aldesleukin) at a dosage of 600,000 IU/kg every 8 to 12 hours for up to 6 doses between 3 to 24 hours after infusion to promote cell growth in vivo. The median dose of lifileucel delivered was 21.1× 109 viable cells. The median number of IL-2 (aldesleukin) doses delivered was 6.

Iwo ekutanga efficacy metrics aive chinangwa chekupindura mwero (ORR) uye nguva yekupindura (DoR). Nguva yepakati yekutanga kuita kune lifileucel yaive mwedzi 1.5. Chidzidzo cheORR chaisanganisira vatori vechikamu makumi manomwe nenhatu vakapihwa lifileucel mukati meyero yakatarwa ye73 x7.5 kusvika 109 × 72 masero anoshanda. Chinangwa chekupindura chiyero (ORR) chaive 109% ine 31.5% nguva yekuvimba (CI) ye95% kusvika 21.1%, uye nguva yepakati yekupindura (DoR) haina kusvika (NR) ine 43.4% CI ye95. NR.

Zvinyorwa zvekurayira zvinosanganisira Yambiro yeBhokisi yerufu rune chekuita nekurapa, cytopenia yakasimba, hutachiona hwakanyanya, nyaya dzemoyo, uye kusagadzikana kwetsvo. Mhedzisiro inowanzoitika (≥20%) mukudzika kwechiitiko yaive kutonhora, pyrexia, kuneta, tachycardia, manyoka, febrile neutropenia, edema, rash, hypotension, alopecia, hutachiona, hypoxia, uye dyspnea.

Iyo yakakurudzirwa lifileucel dosage inotangira pa7.5 x 10^9 kusvika 72 x 10^9 maseru anoshanda.