FDA Grants Orphan Drug Designation to Novel TIL Therapy for Advanced-Stage Melanoma

The FDA has granted orphan drug designation to ITIL-168 for the treatment of stage IIB to IV melanoma, an investigational, autologous cell therapy derived from tumor-infiltrating lymphocytes.

The FDA has granted orphan drug designation to ITIL-168 for the treatment of stage IIB to IV melanoma, an investigational, autologous cell therapy derived from tumor-infiltrating lymphocytes (TILs), announced Instil Bio, Inc, in a press release.1

“The Orphan Drug Designation incentivizes biotech companies to develop new therapies that are important for patients. We are pleased to advance development of ITIL-168 for the treatment of melanoma stages IIB to IV with this designation,” said Bronson Crouch, chief executive officer, Instil Bio, Inc.

Results from a retrospective study assessing the feasibility of using TILs for the treatment of 21 patients with advanced cutaneous melanoma were recently presented at the American Association for Cancer Research (AACR) Annual Meeting 2021. TIL products were administered at 600,000-720,000 IU/kg on a compassionate use basis after the combination of cyclophosphamide 60 mg/kg/day for 2 days and fludarabine 25 mg/m2/day for 5 days. To receive treatment, patients in the study were hospitalized.2

The efficacy of TIL therapy was locally assessed by CT/MRI in accordance with RECIST v1.1 criteria. Fifteen out of 21 patients were evaluable to be locally assessed for efficacy. The remaining 6 patients were using non–RECIST 1.1 imaging, like PET imaging and clinical monitoring. Following infusion of TILs, patients were assessed in the hospital for clinically significant adverse events (AEs).

In all evaluable patients (n = 21), best overall responses were observed in 67% of patients. Best responses were complete responses (CRs) for 19% and partial responses (PRs) for 48% of patients. Additionally, stable disease (SD) was observed in 19% of patients, and progressive disease (PD) was seen in 14%. The disease control rate (DCR) for this population was 86%. Among the 15 imaging evaluable patients, 53% of patients achieved a best overall responses, which was a CR for 13%, and a PR for 40%. Twenty percent of patients achieved SD, while 27% had PD. The DCR was 73%. Patients who responded had a median time to response of 1.7 months.

In terms of survival, the median overall survival (OS) in all evaluable patients was 21.3 months (95% CI, 6.8-not evaluable[NE]). In the imaging evaluable population, OS was evaluated in patients who received a best overall response and well as the nonresponders. Among the patients who were imaging evaluable and achieved a CR or PR, the median OS was NE (95% CI, 10.2 months to NE). Among the nonresponders. The median OS observed was 6.5 months (95% CI, 3.4 months to NE).

The depth of response was assessed in 14 patients, and patients who achieved a best overall response also appeared to have deeper responses. This was especially true for patients who achieved a CR. The change in tumor burden from baseline in these patients was close to 100%. There was no improvement in tumor burden for patients who had PD, and minimal improvement of approximately 10% for those who achieved an SD.

At median follow-up of 52.2 months, responses were durable for 23% of the 14 responding patients, lasting greater than 30 months after TIL infusion. At data cutoff, all patients who achieved a CR were alive and disease free.

Treatment-emergent adverse AE (TEAEs) were assessed following TIL infusion. These events were observed in 15% of patients or more. The most common TEAEs in the study were thrombocytopenia (62%), pyrexia (57%), and rigors (43%). No grade 5 TEAES were observed in the study. There were 10 deaths in the study ≥90 days after TIL infusion and before the data cutoff date. Four of the deaths were caused by PD, 1 was due to an AE, and the remaining 5 had an unknown cause of death but had a PD prior to death.

These retrospective data warrant further evaluation of the use of TILs in patients with advanced melanoma in prospective clinical trials. One such study DELTA-1 (EudraCT, 2020-003862-37) is planned to launch later in 2021.


Instil Bio receives orphan drug designation for ITIL-168 in melanoma. News release. April 27, 2021. Accessed April 27, 2021. https://bit.ly/32VcFeq

Hawkin RE, Jiang Y, Lorigan PC, et al. Clinical feasibility and treatment outcomes with unselected autologous tumor infiltrating lymphocyte therapy in patients with advanced cutaneous melanoma. Presented at: 2021 American Association for Cancer Research Annual Meeting; April 10-15, 2021; Virtual. Abstract LB150