FDA Grants Orphan Drug Designation to CF33-hNIS in Cholangiocarcinoma

• Orphan drug designation has been granted to CF33-hNIS (Vaxinia) from the FDA for the treatment of patients with cholangiocarcinoma.
• CF33-hNIS is a novel oncolytic virotherapy under investigation in the MAST trial (NCT05346484).
• In this phase 1 study, experts are assessing CF33-hNIS alone and in combination with pembrolizumab (Keytruda) in patients with metastatic or advanced solid tumors.

The FDA has granted an orphan drug designation to CF33-hNIS, a novel chimeric oncolytic therapy, in cholangiocarcinoma.¹

FDA orphan drug status is granted to encourage the development of treatments for rare diseases affecting fewer than 200,000 individuals in the US. With this designation, Imugene, the sponsor is offered several incentives, including tax credits, potential grant opportunities, exemption from specific administrative fees, and 7 years of market exclusivity following FDA approval.

“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. We are excited to continue advancing this program, which has already shown meaningful clinical responses in patients,” said Leslie Chong, managing director and chief executive officer of Imugene, in a press release.

Human Liver Anatomy: © nerthuz - stock.adobe.com

CF33-hNIS is a genetically engineered oncolytic virus that is encoded with the hNIS transgene. The agent aims to both reduce the replication of the virus in normal cells and produce selective replication in cancer cells, which leads to tumor cell lysis.²

The phase 1 MAST trial is currently evaluating as CF33-hNIS alone and when combined with pembrolizumab for the treatment of patients with metastatic or advanced solid tumors.³ Enrollment in the study is open to patients aged 18 years and older with a metastatic or advanced solid tumor. Patients are required to have documented radiological progression after treatment with 2 or more prior lines of therapy, which could have included an immune checkpoint inhibitor; at least 1 measurable lesion; an ECOG performance status of 0 to 2; and adequate renal, liver, and hematologic function.

In the dose escalation portion of the study, patients will receive CF33-hNIS intravenously or intratumorally at 1 of 7 doses, ranging from 8.6 x 10⁵ plaque-forming units (PFU) to 3 x 10⁹ PFU on days 1 and 8 of the first 21-day cycle, then on day 1 of each cycle after. Experts also will assess CF33-hNIS with pembrolizumab where pembrolizumab is being given once every 3 weeks starting on day 1 of cycle 2.

Safety and identifying the recommended phase 2 dose are the primary end points of the study, and secondary end points are overall response rate (ORR) per RECIST 1.1 and iRECIST criteria and assessing viral replication in tumor lesions via single-photon emission computerized tomography.

Previous findings from the trial showed that in the monotherapy arm (n = 7), patients had an ORR of 14% and a disease control rate of 86%. An immunological complete response by the fourth cycle of treatment was seen in 1 patient with cholangiocarcinoma. This patient had no known recurrence after 1 year. Additionally, another patient with bile duct cancer had stable disease for more than 5 months.²

For safety, CF33-hNIS given alone was well tolerated with no dose-limiting toxicities reported. No patients discontinued treatment due to treatment-related adverse effects (TRAEs). The most commonly reported TRAEs were pyrexia (grade 1, 14.3%; grade 2, 28.6%), fatigue (0%; 14.3%), injection site pain (14.3%; 0%), folliculitis (0%, 14.3%), pneumonia (0%; 14.3%), pustular rash (14.3%; 0%), muscle spasms (0%; 14.3%), myalgia (0%; 14.3%), lymphadenopathy (14.3%; 0%), vomiting (14.3%; 0%), decreased appetite (14.3%; 0%), headache (0%; 14.3%), blister (14.3%; 0%), and erythema (14.3%; 0%). Moreover, there were no grade 3 or higher TRAEs seen.

REFERENCES:

1. Imugene receives orphan drug designation for treatment of bile tract cancer. News release. Imugene. September 18, 2024. Accessed September 18, 2024. https://tinyurl.com/24ux67rp

2. Li D, Shields AF, Mamdani H, et al. Oncolytic virus CF33-hNIS monotherapy for the treatment of gastrointestinal (GI) malignancies. J Clin Oncol. 2024;42(suppl 3):749. doi:10.1200/JCO.2024.42.3_suppl.749

3. A study of CF33-hNIS (Vaxinia), an oncolytic virus, as monotherapy or in combination with pembrolizumab in adults with metastatic or advanced solid tumors (MAST). ClinicalTrials.gov. Updated May 16, 2024. Accessed September 18, 2024. https://clinicaltrials.gov/study/NCT05346484