FDA Grants Orphan Drug Designation to Ilixadencel to Treat Soft Tissue Sarcoma

An Orphan Drug Designation (ODD) was granted by the FDA to ilixadencel as use for the treatment of patients with soft tissue sarcoma (STS), announced Immunicum AB, in a press release.¹

“We continue to build recognition for ilixadencel’s potential and are pleased to announce that in addition to designations for ilixadencel in renal cell carcinoma and hepatocellular carcinoma, we have now received Orphan Drug Designation by the FDA for the treatment of soft tissue sarcoma, which includes GIST,” said Sven Rohmann, MD, PhD, CEO, Immunicum AB, in a statement.

The ODD was granted in acknowledgment of positive results from the phase 1/2 clinical trial of ilixadencel as treatment of patients with a rare form of sarcoma, gastrointestinal stromal tumors (GIST, NCT02686944).

“GISTs are highly resistant to conventional radio- and chemotherapy and receiving the designation based on the positive data from our phase 1/2 clinical trial provides additional momentum for our pipeline as well as encourages us to bring ilixadencel to patients as rapidly as possible,” Rohmann added, in a statement.

Phase 1 data from 6 patients in the study were presented during the 2020 American Society of Clinical Oncology (ASCO) and Society for Immunotherapy of Cancer (SITC) Clinical Immuno-Oncology Symposium. Patients with progressing advanced or metastatic GIST were administered ilixadencel intratumorally at a maximum dose of 10,000,000 allogeneic dendritic cells/mL per injection despite ongoing treatment with second- or later lines of tyrosine kinase inhibitors (TKIs). Per the study protocol, TKI treatment was stopped if further tumor progression was observed at the 3-month follow-up time point. Patients who achieved an objective response to their TKI treatment or had stable disease (SD) continued on until disease progression. Ilixadencel was injected into tumor lesion at 2 to 3 different time points with ultrasound-guided or CT techniques.²

The coprimary end points of the study were changes in vital sign and lab parameters, as well as adverse events (AEs) per the Common Terminology Criteria for Adverse Events. Secondary end points included tumor response, progression-free survival, change in ECOG performance status, and level of autoimmunization and alloimmunization parameters.

In the initial analysis, no serious AEs were seen with ilixadencel. Tumor progression did occur in 4 patients at 3 months, warranting withdrawal from TKI treatment. In terms of tumor responses, SD by modified RECIST criteria was observed in 2 patients. Notably, one of the patients who was receiving sunitinib (Sutent) in the second line had stable disease through 12 months. The 2 patients with SD had partial responses by Choi criteria, which were sustained for 3 months and 6 months, respectively. In 33% of patients, promising radiological tumor responses were detected.

The safety profile observed with ilixadencel in the cohort of 6 patients was acceptable overall, showing potential for the agent as treatment of patients with advanced GIST who developed resistance to a TKI.

The ODD for ilixadencel in this patient population comes on the heels of a Fast Track designation granted in December 2020, showing the excitement to fill an unmet medical need in the field of STS. Ilixadencel has previously shown promise as monotherapy and in combination regimens in other malignancies. The treatments being investigated in combination with ilixadencel include sunitinib (Sutent), regorafenib (Stivarga), and pembrolizumab (Keytruda). The agent is now moving toward late-stage clinical development.¹

_References:

_{1Immunicum AB (publ) receives FDA Orphan Drug Designation for ilixadencel as a treatment of soft tissue sarcoma (STS). News release. Immunicum AB. January 26, 2021. Accessed January 26, 2021. https://bit.ly/2MqYado}

_{2Karlsson-Parra A, Fröbom R, Berglund E, et al. Phase I trial evaluating safety and efficacy of intratumorally administered allogeneic monocyte-derived cells (ilixadencel) in advanced gastrointestinal stromal tumors. Presented at: Meeting: 2020 ASCO-SITC Clinical Immuno-Oncology Symposium; February 5-8, 2020; Virtual. Abstract 15.}