"We are very pleased to announce our pivotal cohort 4 early data from the C-144-01 clinical study in advanced melanoma today."
Lifileucel (LN-144) showed a favorable overall response rate in patients with pretreated metastatic melanoma, according to initial data from cohort 4 of the phase 2 C-144-01 trial. The developer of lifileucel, Iovance Biotherapeutics, Inc, plans to submit a Biologics License Application to the FDA, based on these findings.1
“We are very pleased to announce our pivotal cohort 4 early data from the C-144-01 clinical study in advanced melanoma today,” said Maria Fardis, PhD, president and CEO of Iovance Biotherapeutics, in a statement.
At a median follow-up of 5.3 months, the objective response rate (ORR) observed in the 68-patient cohort was 32.4%, which included partial responses (PRs) in 21 patients, 2 of which were pending confirmation at data cutoff, and one complete response (CR). The disease control rate (DCR) was 72.1%.
Findings from cohort 4 were consistent with cohort 2 of the study, which is comprised of patients with advanced melanoma who progressed on checkpoint inhibitors and targeted therapies, which was recently presented at the 2020 American Society of Clinical Oncology (ASCO) Virtual Annual Meeting.
The investigator-assessed ORR for cohort 2 was 36.4%, which included one [LA1] CR (3.0%) and 22 PRs (33.3%). In addition, 29 patients had stable disease (43.9%) and 9 patients had progressive disease (13.6%). After a median follow up of 18.7 months (range, 2.2-26.9+) the DCR was 80.3%, and responses occurred regardless of the location of the resected tumor. Notably, responses with lifileucel in cohort 2 deepened over time. The results also showed a mean time to response of 1.9 months (range, 1.3-5.6). The median duration of response had not yet been reached after a median follow-up of 18.7 months.2
Baseline characteristics were similar between cohorts 2 and 4. The baseline disease burden was high. All patients had prior progression on multiple therapies, including BRAF/MEK inhibitors.
The adverse event (AE) profiles were also similar. Cohort 2 showed a profile consistent with the underlying advanced disease and what is known of treatment with lymphodepletion and interleukin-2 regimens. The most common any-grade AEs observed were thrombocytopenia (89.4%), chills (80.3%), and anemia (68.2%). The most common grade 3 and 4 AEs were thrombocytopenia (81.8%), anemia (56.1%), and febrile neutropenia (54.5%). The AEs observed in cohort 4 in addition to updated efficacy data will be presented at an upcoming medical meeting.
C-144-01 is a multicenter study evaluated the efficacy and safety of lifileucel in patients with metastatic melanoma. There are 4 cohorts in the study in which patients received different forms of tumor-infiltrating lymphocyte (TIL) therapy. The 30 patients in cohort 1 received non-cryopreserved TILs, the 60 patients in cohort 2 received cryopreserved TILs, the 10 patients in cohort 3 were given TIL re-treatment, and the 75 patients in cohort 4 received second-generation cryopreserved TILs.1,2
The primary end point of the ongoing study is efficacy defined by ORR. The secondary end points are duration of response, DCR, progression-free survival, overall survival, and the AE incidence rate. Patients are eligible to enroll in the C-144-01 trial if they have one resectable tumor lesion and one or more tumor lesions as a target for RECIST 1.1 assessment. Patients are required to be 18 to 70 years of age with an ECOG performance status of 0 or 1.
The study is ongoing and all cohorts have completed recruitment.
1. Iovance reports pivotal cohort 4 data for tumor infiltrating lymphocyte (TIL) therapy lifileucel from C-144-01 clinical study in advanced melanoma. News release. Iovance Biotherapeutics, Inc. May 27, 2020. Accessed June 1, 2020. https://bit.ly/2ZZzM7o
2. Sarniak A, Khushalani NI, Chesney JA, et al. Long-term follow up of lifileucel (LN-144) cryopreserved autologous tumor infiltrating lymphocyte therapy in patients with advanced melanoma progressed on multiple prior therapies.J Clin Oncol. 2020;38(suppl):10006. doi: