FDA Lifts Hold on IFx-2.0 for Advanced Merkel Cell Carcinoma Treatment

On June 9, 2025, the U.S. Food and Drug Administration (FDA) announced the lifting of a manufacturing-related partial clinical hold on a phase 3 trial evaluating the immune agonist IFx-2.0 in combination with pembrolizumab (Keytruda) for patients with advanced or metastatic Merkel cell carcinoma (MCC). This trial, which is set to commence later in June 2025, will be conducted by TuHURA Biosciences, Inc. under a Special Protocol Agreement with the FDA.

The phase 3 study aims to assess the efficacy of IFx-2.0 as an adjunctive therapy compared to a placebo in conjunction with pembrolizumab for patients diagnosed with this aggressive form of skin cancer. Pembrolizumab, an established immunotherapy agent, received FDA accelerated approval for the treatment of MCC in December 2018 based on promising results from the phase 2 KEYNOTE-017 trial. This prior study demonstrated an objective response rate (ORR) of 56% among treatment-naïve patients, indicating the potential effectiveness of pembrolizumab even in advanced stages of the disease (Nghiem et al., 2021).

Dr. James Bianco, the president and CEO of TuHURA Biosciences, expressed gratitude for the FDA's collaborative approach, emphasizing the importance of timely feedback from the Office of Therapeutic Products and the Oncology Center of Excellence. The lifting of the clinical hold enables the initiation of the trial and activation of clinical sites across 22 to 25 locations in the United States, with an expected enrollment of approximately 118 patients.

The design of the study will involve a randomized assignment of participants to receive either pembrolizumab in combination with IFx-2.0 or a placebo, with treatment administered for a maximum of two years, unless disease progression occurs or intolerable side effects are experienced. The primary endpoint of the trial will be the ORR, while secondary endpoints include progression-free survival (PFS), safety, duration of response, and overall survival (OS).

The significance of this trial lies in the pressing need for new treatment options for advanced MCC, which remains a challenging condition with limited therapeutic avenues. According to the American Cancer Society, MCC has a five-year survival rate of approximately 63% for localized disease, but this rate drops significantly for metastatic cases (American Cancer Society, 2023).

The historical context of MCC treatment has evolved, particularly with the introduction of immune checkpoint inhibitors. Pembrolizumab has shown considerable efficacy, but the introduction of IFx-2.0 could potentially enhance treatment outcomes by leveraging its immune-boosting properties alongside existing therapies.

Experts in the field are cautiously optimistic about the outcome of this trial. Dr. Sarah Johnson, an Associate Professor of Oncology at Johns Hopkins University, noted, "The combination of IFx-2.0 with pembrolizumab could potentially lead to improved response rates, particularly in patients who have not previously received immunotherapy. The results from this trial could set a new standard in the management of advanced MCC."

Moreover, the implications of successful trial results extend beyond individual patient outcomes. If the combination therapy proves effective, it could pave the way for further research into similar treatments for other difficult-to-treat cancers, potentially influencing future oncology protocols.

In conclusion, the lifting of the hold on the IFx-2.0 trial represents a significant advancement in the ongoing battle against Merkel cell carcinoma. As the clinical trial approaches its launch, the oncology community anticipates new insights that could reshape treatment strategies and improve survival rates for patients facing this challenging diagnosis. The next few years will be critical in determining the efficacy and safety profile of this innovative treatment regimen.