The FDA has granted orphan drug designation to CF33-hNIS (Vaxinia), a novel oncolytic virotherapy developed by Imugene, for the treatment of cholangiocarcinoma. This designation aims to encourage the development of new treatments for this rare and aggressive cancer affecting fewer than 200,000 individuals in the U.S.
CF33-hNIS: A Novel Oncolytic Virotherapy
CF33-hNIS is a genetically engineered oncolytic virus designed to selectively replicate in cancer cells, leading to tumor cell lysis while minimizing harm to normal cells. The virus is encoded with the human sodium iodide symporter (hNIS) transgene. It is currently being evaluated in the phase 1 MAST (Metastatic Advanced Solid Tumors) trial (NCT05346484) as a monotherapy and in combination with pembrolizumab (Keytruda) for patients with metastatic or advanced solid tumors.
Leslie Chong, managing director and chief executive officer of Imugene, stated, "Receiving orphan drug designation from the FDA is a major milestone for us. It reflects the potential of [CF33-hNIS] to address the urgent need for new treatments for cholangiocarcinoma, a disease with limited therapeutic options."
Clinical Trial: MAST (NCT05346484)
The phase 1 MAST trial is enrolling patients aged 18 years and older with metastatic or advanced solid tumors who have experienced documented radiological progression after at least two prior lines of therapy, which may have included an immune checkpoint inhibitor. Key inclusion criteria include an ECOG performance status of 0 to 2, at least one measurable lesion, and adequate renal, liver, and hematologic function.
In the dose escalation portion of the study, patients receive CF33-hNIS intravenously or intratumorally at doses ranging from 8.6 x 10^5 to 3 x 10^9 plaque-forming units (PFU) on days 1 and 8 of the first 21-day cycle, and then on day 1 of each subsequent cycle. The combination arm involves CF33-hNIS with pembrolizumab, administered once every three weeks starting on day 1 of cycle 2.
The primary endpoints of the study are safety and identification of the recommended phase 2 dose. Secondary endpoints include overall response rate (ORR) per RECIST 1.1 and iRECIST criteria, and assessment of viral replication in tumor lesions via single-photon emission computerized tomography.
Promising Early Results
Previous findings from the MAST trial showed that in the monotherapy arm (n = 7), patients had an ORR of 14% and a disease control rate of 86%. One patient with cholangiocarcinoma experienced an immunological complete response by the fourth cycle of treatment and had no known recurrence after one year. Another patient with bile duct cancer had stable disease for more than five months.
CF33-hNIS monotherapy was well tolerated, with no dose-limiting toxicities reported. The most common treatment-related adverse events (TRAEs) were generally mild, including pyrexia (grade 1, 14.3%; grade 2, 28.6%) and fatigue (0%; 14.3%). No patients discontinued treatment due to TRAEs, and no grade 3 or higher TRAEs were observed.
Implications of Orphan Drug Designation
The FDA's orphan drug designation provides Imugene with several incentives to support the development of CF33-hNIS, including tax credits, potential grant opportunities, exemption from certain administrative fees, and seven years of market exclusivity following FDA approval. This designation underscores the potential of CF33-hNIS to address the unmet medical need in cholangiocarcinoma and accelerate its development towards potential clinical use.
