Lifileucel/Pembrolizumab Elicits Encouraging ORR in ICI-Naïve Advanced Melanoma

The addition of lifileucel to pembrolizumab resulted in an overall response rate of 85.7% compared with pembrolizumab alone in patients with immune checkpoint inhibitor–naïve advanced melanoma.

The addition of lifileucel (LN-144) to pembrolizumab (Keytruda) resulted in an overall response rate (ORR) of 85.7% compared with pembrolizumab alone in patients with immune checkpoint inhibitor (ICI)–naïve advanced melanoma, according to data from the phase 2 IOV-COM-202 trial (NCT03645928) presented during the 2021 ASCO Annual Meeting.

“Advanced melanoma remains a significant health burden with a high unmet clinical need despite treatment advances in immunotherapy,” said Sajeve Samuel Thomas, MD, lead study author and medical oncologist and hematologist at Orlando Health Cancer Institute. “Lifileucel TIL [tumor-infiltrating lymphocyte]-cell therapy has demonstrated efficacy and durability of response in patients with advanced metastatic melanoma who have progressed while on or following treatment with anti-PD-1 or PD-L1 therapy.”

Researchers in the phase 2, multicenter, multi-cohort, open-label study enrolled 7 patients with ICI-naïve advanced melanoma (unresectable or metastatic) as of February 14, 2021. Five of the 7 patients were treatment-naïve, while 1 patient received prior treatment with BRAF inhibitors and MEK inhibitors and the other patient received prior chemotherapy.

In addition, 71% of patients had liver/brain lesions and 43% had lactate dehydrogenase levels greater than the upper limit of normal. The mean target lesion sum of diameter was 111.4 mm, with 85.7% of patients having a more than 3 target and non-target lesions, “representing advanced disease at baseline for this patient group,” Thomas said.

“The primary efficacy endpoint was investigator-assessed objective response rate using RECIST version 1.1, while the primary safety endpoint measured the incidence of grade 3 or higher treatment-emergent adverse events,” Thomas explained.

Lifileucel is generated at centralized good manufacturing practice facilities during a 22-day process. Researchers administered a nonmyeloablative lymphodepletion using cyclophosphamide and fludarabine before a single infusion of lifileucel. This was followed by no more than 6 doses of lifileucel at 600,000 IU/kg.

Patients were followed-up for a median of 8.2 months, and the mean number of TIL cells infused into patients was 27.3 billion.

Six patients had a confirmed objective response to the treatment. In particular, 1 patient had a complete response, and 5 patients had a partial response. Three patients who originally responded to therapy were no longer taking pembrolizumab due to adverse events at 3 months, 4 months and 13 months, although they continue to have a maintained response.

Of note, the longest duration of response was 16.8 months. The complete response rate was 42.9%.

Treatment-related adverse events occurred in at least 30% of patients in the study and included thrombocytopenia, chills, nausea, pyrexia, vomiting, fatigue, febrile neutropenia, hypertension, neutropenia, alopecia, cough, decreased appetite and peripheral edema. This adverse event profile was consistent with the underlying disease and the known adverse effect profiles of nonmyeloablative lymphodepletion, pembrolizumab and lifileucel. There were no grade 5 treatment-emergent adverse events during this study, and unexpected toxicity was seen in patients related to pembrolizumab after TIL therapy.

“We are encouraged by this data confirming the potential feasibility and activity of combination lifileucel and pembrolizumab in the early-line treatment of patients with advanced metastatic melanoma,” Thomas concluded.

Enrollment to the IOV-COM-202 trial is ongoing.


Thomas SS, In KG, Doger B, et all. Safety and efficacy of lifileucel (LN-144), an autologous, tumor infiltrating lymphocyte cell therapy in combination with pembrolizumab for immune checkpoint inhibitor naïve patients with advanced melanoma. J Clin Oncol. 2021;39(suppl 15):9537. doi:10.1200/JCO.2021.39.15_suppl.9537