In a cohort of a phase II study reported in the Journal of Clinical Oncology, Amod A. Sarnaik, MD, and colleagues found that the tumor-infiltrating lymphocyte therapy lifileucel produced durable responses in patients with metastatic melanoma previously treated with checkpoint inhibitors and BRAF- and/or MEK-targeted agents.

Lifileucel is an autologous centrally manufactured tumor-infiltrating lymphocyte product.

Amod A. Sarnaik, MD

Study Details

Sixty-six evaluable patients (cohort 2) were enrolled into the international, multicenter, multicohort trial between April 2017 and January 2019. Patients had received a mean of 3.3 prior therapies, including PD-1 or PD-L1 inhibitors in 100%, cytotoxic T-lymphocyte–associated protein-4 inhibitor therapy in 80%, and BRAF and/or MEK inhibitors in 23% who had BRAF V600 mutation–positive disease.

Lifileucel was produced from harvested tumor specimens in central facilities using a 22-day process. Patients received a nonmyeloablative lymphodepleting regimen with cyclophosphamide and fludarabine. A single infusion of lifileucel at 1 × 10⁹ to < 150 × 10⁹ cells was given approximately 24 hours after the last dose of fludarabine, with patients receiving up to six doses of high-dose interleukin-2. The primary endpoint was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1.

Responses

The mean number of tumor-infiltrating lymphocyte cells infused was 27.3 × 10⁹ (range = 1.2 × 10⁹–99.5 × 10⁹). Objective response was observed in 24 patients (36%, 95% confidence interval [CI] = 25%–49%), with complete response in 2. An additional 29 patients (44%) had stable disease. The disease control rate was 80% (95% CI = 69%–89%). Median time to best response was 1.4 months (range = 1.3–8.7 months). Median duration of response was not reached (range = 0.2–34.1 months) after a median follow-up of 18.7 months; response duration of ≥ 1 year was observed in 69% of responders.

Median overall survival was 17.4 months (95% CI = 11.0 months–not reached); overall survival of ≥ 1 year was observed in 38% of patients with stable disease and 92% of those with objective response.

Among 42 patients with primary refractoriness to PD-1 or PD-L1 inhibitor therapy, objective response was observed in 17 patients (41%, 95% CI = 26%–57%), including complete response in 2. An additional 17 patients (41%) had stable disease; the disease control rate was 81% (95% CI = 66%–91%). Median duration of response was not reached.

Adverse Events

The safety profile was consistent with known adverse events associated with nonmyeloablative lymphodepletion and interleukin-2. The most common grade 3 or 4 adverse events were thrombocytopenia (82%), anemia (56%), febrile neutropenia (55%), neutropenia (39%), hypophosphatemia (35%), leukopenia (35%), and lymphopenia (32%). The incidence of adverse events, including grade 3 or 4 events, decreased rapidly over time, with no lifileucel-related serious adverse events being reported after 6 months and no recurrences of immune-related adverse events related to prior checkpoint inhibitor therapy being observed. Adverse events led to death in two patients; one death due to intra-abdominal tumor hemorrhage was considered possibly related to lifileucel, and one death due to acute respiratory failure was not considered related to lifileucel.

The investigators concluded, “Lifileucel demonstrated durable responses and addresses a major unmet need in patients with metastatic melanoma with limited treatment options after approved therapy, including the primary refractory to anti–PD-1 or PD-L1 therapy subset.”

Dr. Sarnaik, of the Department of Cutaneous Oncology, Moffitt Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Iovance Biotherapeutics Inc. For full disclosures of the study authors, visit ascopubs.org.