Novel TIL Therapy With Keytruda May Improve Treatment Responses in Advanced Skin Cancer


Lifileucel with Keytruda may lead to an improved overall response rate of 86% for patients with advanced melanoma who were pre-checkpoint inhibitor naïve compared with those treated with Keytruda alone.

A novel tumor-infiltrating lymphocyte (TIL) therapy, lifileucel, plus Keytruda (pembrolizumab) increased the overall response rate in patients with pre-immune checkpoint inhibitor (ICI)-naïve advanced melanoma compared with Keytruda alone.

“Advanced melanoma remains a significant health burden with a high unmet clinical need despite treatment advances in immunotherapy,” said Dr. Sajeve Samuel Thomas, lead study author and medical oncologist and hematologist at Orlando Health Cancer Institute in Florida, in a presentation at the 2021 ASCO Annual Meeting. “Lifileucel TIL-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.”

In particular, TIL therapy is a type of treatment where a type of immune cell (lymphocytes) are removed from a patient’s tumor, grown in large numbers at a laboratory then infused back into the patient to help their immune system kill cancer cells.

In this phase 2 study, researchers enrolled seven patients with ICI-naïve advanced melanoma (unresectable or metastatic). Five of the seven patients were treatment-naïve, while one 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 (which indicate tissue damage) greater than the upper limit of normal.

Lifileucel is generated at centralized good manufacturing practice facilities during a 22-day process. Researchers administered a nonmyeloablative lymphodepletion (a less aggressive chemotherapy that prolongs the persistence of infused cells and increases the effectiveness of tumor treatment) using cyclophosphamide and fludarabine before a single infusion of lifileucel. This was followed by no more than six doses of lifileucel.

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 response with an overall response rate (percentage of patients with a partial or complete response to treatment) of 86%. In particular, one patient had a complete response (no cancer detected after treatment) and five patients had a partial response. Three patients who originally responded to therapy were no longer taking Keytruda due to side effects at three months, four 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 side effects occurred in at least 30% of patients in the study and included thrombocytopenia (low blood platelet count), chills, nausea, fever, vomiting, fatigue, hypertension (high blood pressure), neutropenia (low white blood cell levels), hair loss, cough, decreased appetite and swelling of the legs or arms. These side effects were consistent with the underlying disease and the known side effect profiles of nonmyeloablative lymphodepletion, Keytruda and lifileucel. There were no extreme treatment-emergent side effects during this study.

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

Of note, enrollment into the IOV-COM-202 trial is ongoing.

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