TIL Therapy Lifileucel Shows Sustained Efficacy for Advanced Melanoma

Jason A. Chesney, MD, PhD

The tumor-infiltrating lymphocyte (TIL) therapy lifileucel (LN-144) elicited an objective response rate of 36.4% with a median duration of response that was not yet reached at 28.1 months for patients with advanced melanoma, according to updated findings from cohort 2 of the phase 2 C-144-01 trial presented during the virtual 2021 AACR Annual Meeting.

At the 28.1-month median follow-up, 4.5% of patients experienced a complete response and 31.8% had a partial response. Additionally, 43.9% had stable disease for a disease control rate of 80.3%. Patients had received multiple therapies prior to entering the study, including PD-1 inhibitors and targeted therapies, if appropriate.

“Melanoma patients who have progressed on immune checkpoint and BRAF/MEK inhibitors are among the most challenging patients for oncologists to treat," Jason A. Chesney, MD, PhD, chief of the Division of Medical Oncology and Hematology and director of the James Graham Bron Cancer Center, University of Louisville in Kentucky, said in a statement. "The updated results of the C-144-01 study continue to demonstrate that autologous tumor infiltrating lymphocytes induce durable clinical responses in 36 percent of patients in the study. This study also creates opportunities for additional trials of TILs in many other cancer types and in combination with immunomodulatory agents.”

Lifileucel consists of autologous TILs that are harvested from tumor resections. The TILs are then expanded ex vivo and administered, once a sufficient number of cells has been reached. In cohort 2 of the study, the cells were cryopreserved. Prior to administration, patients received lymphodepleting chemotherapy and following infusion of the TILs up to 6 doses of high-dose IL-2, to support immune expansion and proliferation.

The open-label C-144-01 trial consists of 4 cohorts, 3 of which are now closed to enrollment. Cohort 2, which was presented at AACR, included 66 patients with unresectable or metastatic melanoma. At baseline, the 66 patients had a median age of 55 (range, 20-79), 56% had an ECOG performance status of 0, 68% had BRAF wild-type disease, and 35% were PD-L1–positive (tumor proportion score ≥5). The mean number of prior therapies was 3.3 (range, 1-9), which included anti–PD-1/PD-L1 therapy in all patients, anti–CTLA-4 therapy in 80%, and BRAF/MEK inhibition in 23%.

Patients in cohort 2 also had a high tumor burden at baseline, Chesney noted during a presentation of the findings, with a mean target lesion size of 10.6 cm in diameter (range, 1.1-34.3). Additionally, 77% had more than 3 target and non-target lesions and 42% had liver and/or brain lesions.

With extended follow-up, 17.7% of patients had further reduction in target lesion size since the prior data cutoff period. A total of 81% of evaluable patients had a reduction in their tumor burden. Of the 24 responders, 79% had previously received ipilimumab (Yervoy) and 4% had a partial response converted to a complete response 2 years following infusion with lifileucel. Overall, 49% of responders were still on the study at data cutoff.

No new safety risks were identified with the longer follow-up. Additionally, the number of treatment-emergent adverse events (TEAE) reduced over time. At least 1 TEAE was observed in all 66 patients and were of grade 3/4 in severity in 97%. Two patients experienced a grade 5 event due to intra-abdominal hemorrhage that was possibly due to TIL therapy in 1 patient and acute respiratory failure not related to TIL therapy in the second patient.

The most common TEAEs of any grade were thrombocytopenia (89.4%), chills (80.3%), anemia (68.2%), pyrexia (59.1%), neutropenia (56.1%), and febrile neutropenia (54.5%). The most common grade 3/4 TEAEs were thrombocytopenia (81.8%), anemia (56.1%), febrile neutropenia (54.5%), and neutropenia (39.4%).

“We are very excited to report our latest cohort 2 melanoma data in an oral presentation at AACR,” Maria Fardis, PhD, president and chief executive officer of Iovance Biotherapeutics, the company developing the TIL therapy, said in a statement. “The data continue to demonstrate durability and depth of our lifileucel TIL therapy response after a one-time treatment, in a difficult to treat patient population with advanced melanoma. We are honored that AACR has chosen our melanoma cohort 2 data to be featured in a clinical trials plenary session.”

In cohort 3 of the study, patients from cohorts 1, 2, and 4 will receive retreatment with lifileucel. At this point, this cohort has enrolled 10 patients and has not yet reported outcomes.