Novel Cancer Vaccine Receives FDA Orphan Drug Designation in Cutaneous Melanoma

The FDA has granted orphan drug designation (ODD) to IFx-2.0 for the treatment of patients with stage IIB to IV cutaneous melanoma, according to a press release from TuHURA Biosciences.¹

The ODD is based on results from an early phase 1 trial (NCT03655756), with previous results being reported in the American Association for Cancer Research Journals.² The study found that IDx-2.0 was safe and led to no serious dose limiting toxicities. Additionally, if patients were refractory to a checkpoint inhibitor therapy, a clinical benefit was experienced during subsequent anti-PD1 based treatment.

"Our current focus with IFx-2.0 is targeting completion of enrollment in our phase 3 study of IFx-2.0 in combination with [pembrolizumab (Keytruda)] for the first-line treatment of advanced or metastatic Merkel cell carcinoma. We believe receiving ODD in advanced cutaneous melanoma demonstrates not only the significant need for new treatments in skin cancer but also highlights IFx-2.0 as a potential new therapeutic approach in this patient population,” James Bianco, MD, president and chief executive officer of TuHURA Biosciences, said in the press release.

Results from the trial showed that 8 patients were screened, and 7 met the eligibility criteria. Patients ages ranged from 60 to 85 years old, and the trial met the primary end point. This included 6 patients who completed the dose limiting toxicity (DLT) period and did not experience any DLTs relating to IFx-2.0. Grade 1/2 toxicities were noted and deemed related to IFx-2.0; they were expected from intralesional injection but were managed.

Adverse effects (AEs) included 5 patients who had grade 1/2 injection site reactions, 1 patient had grade 1 bleeding, 1 patient had grade 1/2 pain, 1 patient had grade 1 lymphopenia, and 1 patient had grade 1 pruritus. No grade 3/4 AEs were noted. There was 1 grade 5 toxicity from Clostridium septicum infection that occurred 20 days after the treatment injection. After investigation this was deemed unrelated to the study.

Stable disease was noted in 3 patient, and 3 patients progressed per RECIST 1.1 at the time of the 30-day follow-up visit. Pre- and post-therapy, lactate dehydrogenase values were within the normal limits for all evaluable patients, and there were no significant differences in neutrophil or lymphocyte ratios.

After initial therapy ended, 6 patients received further anticancer therapy. After post-protocol treatment with an anti-PD1-based therapy, 3 of 4 patients who were anti-PD1 refractory demonstrated a clinical benefit. This included stable disease lasting more than 2 years followed by surgical resection with progression-free survival post-protocol therapy (PFS2) of more than 3.66 years, PFS2 of 1.08 years, and a partial response that was surgically resected and showed no evidence of disease with a PFS2 of 1.66 years.

Ifx-2.0 was injected at 0.1 mg into cutaneous lesions of patients 18 years or older who had melanoma. For patients to be enrolled, they needed at least 2 injectable lesions of 3 mm or greater. Patients who had brain metastases of 1 cm or less were permitted into the study, but under the notion that they had a longer than 3-month life expectancy, and if they had received radiation, it was distant from the injection site.

If patients tolerated the first dose and showed no evidence of progression, patients could continue dosing every 3 weeks. The success of the study was hinged upon treating 5 of 6 patients without DLTs at 28 days.

“In this trial, IFx-Hu2.0 was shown to be safe to inject into melanoma lesions, and there were no DLTs attributable to IFx-Hu2.0. The data from clinical trial specimens suggest that IFx-Hu2.0 acting through the interferon response and Toll-like receptors can be an active bridge between the innate and adaptive immune responses by activating interferon pathways and promoting antigen recognition of Emm55 peptides…. Posttreatment evidence of clinical benefit for retreatment with anti-PD1 antibodies in 3 patients previously refractory to those agents is encouraging and suggests the possibility of synergy if IFx-Hu2.0 is administered in conjunction with immunotherapy,” lead study author Joseph Markowitz, MD, PhD, associate member in the Department of Cutaneous Oncology at the H. Lee Moffitt Cancer Center & Research Institute, and associate professor in the Department of Oncologic Sciences of Morsani College of Medicine at the University of South Florida, and colleagues wrote in the paper.

References

1. TuHURA Biosciences received FDA orphan drug designation for IFx-2.0 for the treatment of stage IIB to stage IV cutaneous melanoma. News release. TuHURA Biosciences. February 2, 2026. Accessed February 2, 2026. https://tinyurl.com/mpj83hsm
2. Markowitz J, Shamblott M, Brohl AS, et al. First-in-human stage III/IV melanoma clinical trial of immune priming agent IFx-Hu2.0. Mol Cancer Ther. 2024;23(8):1139-1143. doi:10.1158/1535-7163.MCT-23-0652