IFx-Hu2.0: A Potential Breakthrough for Skin Cancers

Cutaneous squamous cell carcinoma - Generated with Google Gemini AI

Patients with advanced Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (cSCC) have limited treatment options, especially after failing immunotherapy. Because of this, a recent study (NCT04160065) evaluated the safety and efficacy of IFx-Hu2.0, a novel cancer vaccine, in these patients.

The vaccine was well-tolerated and could be safely administered multiple times. The most promising finding was the 56% response rate to subsequent immunotherapy treatment in patients with MCC. This suggests that IFx-Hu2.0 may be able to prime the immune system, allowing for a second chance at immunotherapy even after initial failure.

While further research is needed, these results offer hope for patients with these difficult-to-treat cancers.

In an interview with Targeted Oncology^TM, Andrew Brohl, MD, medical oncologist and physician-scientist at Moffitt Cancer Center, discusses the findings from the study and the future of this research.

Andrew Brohl, MD

Targeted Oncology: What are the unmet needs in this patient population that this study focused on?

Brohl: This study was focused on advanced Merkel cell carcinoma as well as cutaneous squamous cell carcinoma, and it focused on the population that has failed standard-of-care anti-PD-1 or anti-PD-L1 immunotherapy.

Can you explain how this vaccine works?

This is an intralesional product injected directly into 1 or more of the tumors that the patient has. It is designed to have a bacterial antigen from streptococcus bacteria and the transfection agent. When this gets in proximity to the cancer cells, the bacterial antigen starts expressing it on the cell surface. This should elicit an immune response from the body since it is a strong antigen. This draws the immune system in towards the tumor and, ideally, sparks an immune response.

What was your study evaluating?

This study was designed as a safety study, as well as to obtain biomarkers for analysis to see if this product actually induces the immune system like we hope it does. Based on those goals of the study, the study was successful. There were no safety signals and low rates of toxicities, mostly just local effects from the injection.

From a biomarker analysis, we have been seeing early signs, although we still need to do some analysis that it is making these potentially cold tumors hotter or having more of an immune attack in the tumors themselves after the injection. But most interesting that was not even part of the original design of the trial was that we saw an interesting efficacy signal where we took these patients who had previously failed standard-of-care checkpoint inhibitor therapy then went on this trial. After they completed this series of injections, we put them back on the same exact drug class before, and many of them experienced a durable and pronounced response to the same drug class that they were previously refractory to.

Based on this early research, are there any takeaways for colleagues?

I think the takeaway is that there is an exciting early efficacy signal of this agent, especially as used as an immune priming agent to give a better success rate to immune checkpoint inhibitors. Based on this early signal, we are planning a follow-up study with the same agent to do a randomized trial with the registrational design. This will be exciting for our field in Merkel cell carcinoma where we are pursuing this. At the time that it opens, it will be the largest trial in this rare cancer.

What do you think the future of cancer vaccines looks like in skin cancer?

It is an area of active investigation in several different agents that [researchers] are looking at to try to find best ways to prime the immune system against these cancers. For Merkel cell carcinoma, specifically where there is strong antigen burden from either the [ultraviolet] mutagenesis or from the Merkel cell virus, I think it is a good area to explore as a therapeutic option for these patients.

REFERENCE:

Brohl A, Silk A, Thomas S, et al. Phase 1b trial of IFx-Hu2.0, a novel in situ cancer vaccine, in checkpoint inhibitor-resistant Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (cSCC). J Clin Oncol. 2024;42(suppl 16)abstr 9592. doi: 10.1200/JCO.2024.42.16_suppl.9592