ITIL-168 Receives Orphan Designation for Melanoma

The FDA has granted an orphan drug designation to ITIL-168 as a potential treatment for patients with stage IIB to IV melanoma, according to a statement from Instil Bio, the developer of the tumor infiltrating lymphocyte (TIL) therapy.

In late breaking e-poster findings from 21 patients in a phase 1 study that were presented at the 2021 AACR Annual Meeting, ITIL-168 was shown to elicit a 67% objective response rate (ORR) in patients with metastatic melanoma. This included a complete response rate of 19%. A phase 2 study for the therapy is expected to begin later this year.

“This presentation highlights the potential for ITIL-168 to produce deep and durable remissions in patients with advanced melanoma,” Bronson Crouch, chief executive officer of Instil, said in a statement when the AACR data were presented in early April 2021. “We eagerly anticipate beginning a global phase 2 clinical trial investigating ITIL-168 for the treatment of advanced melanoma later this year.”

The orphan drug designation is intended for products that treat rare diseases or conditions and was established under the Orphan Drug Act. The designation provides several incentives, according to the FDA, including tax credits for qualified clinical testing. Moreover, a company developing an orphan product is not required to pay prescription drug user fees when submitting a marketing application for the designated indication.

“The orphan drug designation incentivizes biotech companies to develop new therapies that are important for patients," said Crouch. “We are pleased to advance development of ITIL-168 for the treatment of melanoma stages IIB to IV with this designation.”

ITIL-168 is an autologous cell therapy manufactured from patients’ TILs, which are collected from a tumor resection. In the process, the tumor tissue is completely digested at the site of the resection to release all TILs. The resulting cells are cryopreserved and then sent to a manufacturing facility, to be optimized and expanded. Prior to infusion of ITIL-168, the patient is lymphodepleted with cyclophosphamide and fludarabine. After the TIL infusion, IL-2 is infused for up to 12 doses to improve proliferation.

The median duration of follow-up at the AACR presentation was 52.2 months. The median number of TIL cells infused was 32 x 10^9 and IL-2 was administered for a median of 8 doses. The median age of patients was 45 years, and all had metastatic disease. Prior to entering the study, patients had received a mean of 3 prior therapies, including immune checkpoint inhibitors (91%).

In addition to the ORR of 67%, 19% of patients also experienced stable disease following treatment with ITIL-168, bringing the overall disease control rate (DCR) to 86%. The median time to response was 1.7 months. In those with imaging available (n = 15), the ORR was 53%, which included a complete response rate of 13%. The DCR was 73%.

At the time of the analysis, the median overall survival (OS) was 21.3 months (95% CI, 6.8 to not evaluable [NE]). In those experiencing a response, the median OS was not yet reached, with a lower bound on the confidence interval of 10.2 months. In those with no response, the median OS was 6.5 months (95% CI, 3.4-NE).

The most common treatment-emergent adverse events (TEAEs) of any grade were thrombocytopenia (62%), pyrexia (57%), rigors (43%), neutropenia (29%), tachycardia (29%), pulmonary edema (24%), vascular leak (24%), and rash (19%). There were no grade 5 TEAEs and most cytopenias were related to the lymphodepletion regimen and recovered by 7 days post-TIL infusion.

“Despite the recent advances in immunotherapy for solid tumors, many patients do not receive clinical benefit or experience relapse after an initial remission,” presenting study author Robert Hawkins, MBBS FRCP, PhD, chief strategy advisor to Instil, said in a statement when the data were presented. “In this compassionate use setting in which patients had exhausted all other available therapies, a one-time treatment with TILs was able to induce a remission in more than half of the treated patients.”

Findings from the phase 1 study will be submitted for publication in a peer reviewed journal, the company noted. Instil also released plans to submit findings from the phase 2 study to regulatory agencies, if positive results are reported. The company anticipates enrolling and receiving topline results by 2023 from the phase 2 study of ITIL-168, with a US regulatory submission anticipated for the same year.