Lifileucel showed clinically meaningful activity in patients with advanced mucosal melanoma whose disease had progressed on immune checkpoint inhibitors, according to subgroup data presented at the 2023 ESMO Congress.1
With a median follow-up of 35.7 months, the objective response rate (ORR) was 50% (95% CI, 21.1%-78.9%), 1 patient achieved complete response. Four patients had stable disease and 2 patients had progressive disease (PD). Notably, as of the data cutoff of July 15, 2022, 4 of the 6 responders had sustained and sustained responses.
“Advanced mucosal melanoma is rare and difficult to treat, and responds poorly to anti-PD-1 therapy,” said Evidio Domingo Musibay, MD, assistant professor of medicine in the Division of Hematology, Oncology and Transplantation at the University of Minnesota School of Medicine in Minneapolis, during a presentation Zhong said. “ORR tended to be low, ranging from 19% to 23% (median overall survival (OS) 11.3 to 16.0 months). (In a previous study), lifileucel autologous tumor-infiltrating lymphocyte therapy after extensive pre-testing demonstrated an ORR of 31.4% in patients with advanced melanoma (n = 153).”
Evidio Domingo Musibay, MD
Assistant Professor of Medicine
Hematology, Oncology and Transplantation
University of Minnesota Medical School (Minneapolis)
C-144-01 is a multicenter trial enrolling patients with unresectable or metastatic stage IIIc or IV melanoma whose disease progressed during or after anti-PD-1 therapy. Patients needed to have an ECOG performance status of 1 or less, an expected life expectancy of at least 3 months, and adequate organ function to be eligible for the study.Patients who have received an organ allograft or prior cell transfer therapy, have symptomatic and/or untreated brain metastases, or have Bluff– Mutated disease and no prior BRAF inhibitor treatment were excluded.2
After tumor tissue collection and GMP manufacturing, which takes approximately 22 days, patients receive a non-myeloablative lymphodepletion regimen from days -7 to -6 and fludarabine from days -7 to -6 treatment, then received fludarabine from day -5 to day -1. Patients received an infusion of lifileucel on day 0, followed by IL-2 on days 0 to 4. After treatment, efficacy follow-up continued until the patient developed PD or started new treatment. 1
The primary endpoint is ORR. Secondary endpoints include duration of response (DOR), disease control rate, progression-free survival, overall survival, and incidence of adverse events (AEs).2
At baseline, the median age was 61.5 years (range, 37-79 years), and the median number of previous treatments was 2 (range, 1-6). The majority of patients had primary disease refractory to anti-PD1/L1 therapy (83.3%), 41.7% had liver or brain metastases, and 41.7% had lactate dehydrogenase levels above the upper limit of normal. The median number of target and non-target lesions was 6 (range, 3-13), and the median sum of target lesion diameters was 118.9 mm (range, 20.7-260.9).1
The median IL-2 dose was 5.5 (range, 3-6). Additionally, the median number of tumor-infiltrating lymphocytes infused was 26.1 x 109 cells (range: 3.3 x 109 to 72 x 109).
Additional results from the study indicate that the median DOR (NR; 95% CI, 12.5-NR) has not been reached. All patients had a DOR lasting at least 6 months, 83.3% had a DOR of 12 months or longer, and 66.7% had a DOR of at least 24 months.
Sub-analysis data showed that patients with mucosal melanoma had a lower mean tumor mutation load compared with patients with skin diseases, 2.145 mut/Mb versus 10.47 mut/Mb. In addition, the persistence of tumor-infiltrating lymphocytes over one year was similar in both groups.
Regarding safety, grade 3/4 non-hematologic treatment-emergent AEs (TEAEs) included febrile neutropenia (58.3%), hypotension (33.3%), and hypoxia (16.7%). The most common TEAEs of any grade included chills (75.0%), febrile neutropenia (58.3%), diarrhea (58.3%), and pyrexia (41.7%). Regarding grade 3/4 hematology laboratory abnormalities, all patients had neutropenia, leukopenia, lymphopenia, and thrombocytopenia, and eight patients had anemia.
“The antitumor responses observed in mucosal melanoma were consistent with those observed in the overall population,” Domingo-Musibe said. “TRAE was associated with non-myeloablative lymphocyte depletion and high-dose IL-2. The known safety profile is consistent. These results further support the potential benefits of lifileucel as a one-time treatment that is distinct from other immunotherapies.”
refer to
1. Grigoleit GU, Kluger H, Thomas S, et al. Lifileucel tumor-infiltrating lymphocyte (TIL) cell therapy in patients (pts) with advanced mucosal melanoma after progression on immune checkpoint inhibitors (ICI): results from the phase II C-144-01 study. Ann Anker. 2023;34(Supplement 2):S654. doi:10.1016/j.annonc.2023.09.2220
2. Study of lifileucel (LN-144) (autologous tumor-infiltrating lymphocytes) in patients with metastatic melanoma (LN-144). clinicaltrials.gov. Updated July 12, 2023. Accessed October 21, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT02360579