Study Finds Lifileucel Active in Advanced Melanoma After Disease Progression on Immune Checkpoint Inhibitors

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Cell therapy with tumor-infiltrating lymphocytes (TIL) may address an important unmet need for patients with difficult-to-treat melanoma after disease progression on immune checkpoint inhibitors, according to data presented during the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting.1

Pooled analysis of consecutive cohorts from the C-144-01 study showed an overall response rate of 31.4% to TIL cell monotherapy with lifileucel in heavily pretreated patients with advanced melanoma and a high tumor burden who experienced disease progression on immune checkpoint inhibitors. In addition, at a median follow-up of 36.5 months, the median duration of response was not reached, and 41.7% of responders had a duration of response of at least 2 years. Responses were also observed across subgroups, including those with immune checkpoint inhibitor primary-resistant disease, the authors of the study reported.

“Lifileucel demonstrated clinically meaningful and durable efficacy with an expected and manageable safety profile,” said lead study author Amod Sarnaik, MD, FACS, a surgical oncologist in the Department of Cutaneous Oncology, Immunology Program, and Melanoma Center of Excellence at Moffitt Cancer Center, Tampa, Florida. “One-time lifileucel TIL cell therapy may be a viable option for patients with advanced melanoma who lack effective treatment options after initial disease progression on immune checkpoint inhibitors.”

One-time lifileucel TIL cell therapy may be a viable option for patients with advanced melanoma who lack effective treatment options after initial disease progression on immune checkpoint inhibitors.
— Amod Sarnaik, MD, FACS

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As Dr. Sarnaik explained, treatment options for advanced (unresectable or metastatic) melanoma are limited after nonresponse or disease progression on or after immune checkpoint inhibitor and targeted therapy. 

“Autologous TIL cell therapy recognizes and targets a multitude of patient-specific neoantigens to mediate tumor cell death,” said Dr. Sarnaik. He noted that recent phase III data in Europe have shown superior overall response rates with noncryopreserved TIL cell therapy vs ipilimumab.

Study Methods

Lifileucel, an investigational adoptive cell therapy using cryopreserved autologous TIL, has demonstrated potential efficacy in cohort 2 of the C-144-01 study, a multicenter phase II study in advanced melanoma. During the 2022 SITC Annual Meeting, Dr. Sarnaik reported outcomes of lifileucel across cohorts 2 and 4, representing the largest cell therapy study in advanced melanoma in the post–immune checkpoint inhibitor setting.

Cohort 2 enrolled 66 patients, and the registrational cohort 4 enrolled 87 patients. Eligibility criteria were identical for both cohorts, with no limit on the number of prior therapies. All patients received nonmyeloablative lymphodepletion, a single lifileucel infusion, and up to six doses of intravenous bolus interleukin-2, with no further treatment planned. The primary endpoint was independent review–assessed objective response rate by Response Evaluation Criteria in Solid Tumors version 1.1.

Patients were heavily pretreated with a median of three prior lines of therapy. Most patients had primary resistance to prior PD-1 therapy.

TIL Therapy Safe and Effective

As Dr. Sarnaik reported, assessment of treatment-emergent adverse events started at day 0, just after lymphodepletion. The most common nonhematologic treatment-related adverse events were chills, pyrexia (including febrile neutropenia), hypophosphatemia, hypotension, fatigue, and diarrhea. All patients experienced laboratory-assessed grade 3 or 4 leukopenia, lymphopenia, or neutropenia, which is expected given the lymphodepletion in the regimen.

“Most adverse events were transient, ­manageable, and consistent with the known safety profiles of lymphodepletion and interleukin-2,” said Dr. Sarnaik. “The incidence of new adverse events decreased rapidly over the first 2 weeks after lifileucel infusion, which is one of the benefits of treatment not requiring multiple cycles.”

Objective response rate by independent review was 31.4%, including 9 complete responses and 39 partial responses. Lifileucel was manufactured to within specification in 94.7% of patients. The median time from resection to infusion was 33 days. 

Of note, 79% of patients had a reduction in disease, said Dr. ­Sarnaik. Responses to lifileucel were observed across all subgroups analyzed, including BRAF mutational status and PD-L1 tumor proportion score. Results also showed that patients with some target lesion diameters below the median and a normal lactate dehydrogenase level had a greater likelihood of response than those with either or both adverse factors being higher. According to Dr. Sarnaik, this suggests the “earlier use of lifileucel in disease progression may provide a greater benefit for patients.”

“Although 39 of the 48 responders achieved a response at the time of the first disease assessment at 6 weeks, many responses deepened over time, with some late best response conversions,” said Dr. Sarnaik. In addition, he noted, 7 patients who initially had a partial response improved to a complete response, and 10 improved from stable disease to partial response. “Notably, there were two conversions to complete response that occurred more than 2 years after lifileucel infusion without any additional treatment.” 

The median duration of response was not reached, with a median follow-up of 36 months, and 41.7% of responses were maintained for at least 24 months. These data demonstrate the durability of responses with two patients at or beyond 4 years, said Dr. Sarnaik. The median overall survival for the group was 13.9 months, and the 12-month overall survival rate was 54%. 

DISCLOSURE: Dr. Sarnaik has received consulting fees from Iovance Biotherapeutics, Guidepoint, Defined Health, Boxer Capital, Huron Consulting Group, KeyQuest Health Inc, Istari, Rising Tide, Second City Science, Market Access, and Gerson Lehrman Group; has received speaker fees from Society for Immunotherapy of Cancer, Physicians’ Educational Resource (PER) LLC, Medscape, WebMD, and Medstar Health; has received research funding and other support from Iovance Biotherapeutics, Provectus, Prometheus, and Bristol Myers Squibb; and Dr. Sarnaik’s institution has licensed intellectual property related to the proliferation and expansion of tumor-infiltrating lymphocytes to Iovance Biotherapeutics. Dr. Sarnaik is a co-inventor on such intellectual property.


1. Sarnaik A, Lewis K, Kluger H, et al: Lifileucel TIL cell monotherapy in patients with advanced melanoma after progression on immune checkpoint inhibitors and targeted therapy: Pooled analysis of consecutive cohorts (C-144-01 study). 2022 SITC Annual Meeting. Abstract 789. Presented November 10, 2022.


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