Cancer Vaccine IFx-Hu2.0 Confers Immune Priming Effect in Previously Treated MCC and CSCC


The novel personalized cancer vaccine IFx-Hu2.0 was found to be safe and well tolerated with weekly dosing in patients with checkpoint inhibitor–resistant cutaneous squamous cell carcinoma and Merkel cell carcinoma, according to data from an ongoing phase 1b trial.

Andrew S. Brohl, MD

Andrew S. Brohl, MD

The novel personalized cancer vaccine IFx-Hu2.0 was found to be safe and well tolerated with weekly dosing in patients with checkpoint inhibitor–resistant cutaneous squamous cell carcinoma (CSCC) and Merkel cell carcinoma (MCC), according to data from an ongoing phase 1b trial (NCT04160065) presented at the 2023 ASCO Annual Meeting.

In an exploratory post-hoc analysis of the non-randomized, open-label, multi-center trial, 71% (n = 7) of patients who received standard immune checkpoint inhibitor therapy following IFx-Hu2.0 injection experienced a durable objective response despite having progressive disease with immunotherapy prior to enrollment. Further enrollment of 11 patients is planned in the expansion stage of the study, which will evaluate weekly doing of the agent given for 3 cycles.

“These were exciting early responses, as 4 out of 5 patients with MCC [who] were rechallenged [with immunotherapy] had an excellent response, even though their disease did not previously respond [to immunotherapy]. These outcomes make for very encouraging early data and something that we hope to continue to move forward into the pipeline,” lead study author Andrew S. Brohl, MD, said in an interview with OncLive® during the 2023 ASCO Annual Meeting.

In the interview, Brohl discussed early goals of this phase 1b study evaluating the personalized cancer vaccine IFx-Hu2.0, and key safety and efficacy findings that have been reported from this research thus far. Brohl is a member of The Cancer Genome Atlas sarcoma project and a medical oncologist at Moffitt Cancer Center in Tampa, Florida.

OncLive: Could you describe the mechanism by which this agent promotes antitumor response?

Brohl: This is an early phase trial of a relatively new, intratumoral agent that is administered directly into 1 or several patient tumors. The idea is that it is an immune stimulatory molecule. It's a transfection agent linked with a plasma that encodes for a bacterial protein.

The idea is that [once] this gets into the tumor cells, the tumor cells will then start expressing the bacterial protein, causing the immune system to react to the cells, in turn getting exposed to the preexisting tumor antigens that are there. This then sparks immune responses that hopefully can make some of the existing checkpoint inhibitors more potent.

What patient population was evaluated in this study?

We looked at 2 different tumor populations in this study. We looked at MCC and CSCC. Both tumors are moderately responsive to immunotherapy. Therefore a good percentage of patients respond already to the standard PD-1 or PD-L1 therapies. Notably, they're cutaneous tumors often accessible for injection in clinic.

This study was designed with these 2 factors in mind. This study was also [developed to address] the unmet need in patients who don't respond well to standard checkpoint inhibitors and for patients with other tumor types who don't have optimal options.

What were some of the key safety findings that were presented at the 2023 ASCO Annual Meeting?

We found this drug to be extremely safe, and that was the primary end point of this study. We wanted to make sure that repeated dosing of this agent didn't cause any new safety signals that we didn't see in the original first-in-human study. We observed very minimal toxicity with this agent. The injection site reactions were in general very mild and well tolerated and no significant adverse effects [AEs] were seen in this study.

What were the key efficacy findings that were highlighted in the poster presentation?

We saw modest efficacy in terms of some responses in the injected tumor site. However, we did not see any systemic responses from the agent. What was more interesting is that we followed these patients post-protocol. Many of these patients ended up getting rechallenged with the same drug class of anti–PD-1 or anti–PD-L1 [inhibitors] that their disease had not responded to earlier. We saw a significant percentage of these patients that were rechallenged in this fashion achieve an excellent response to a therapy that previously did not work for them.

This suggests somewhat of an immune priming effect from this study therapy that potentially allows for this same drug class to work better the second time around.

What next steps will be taken with this research?

We're very encouraged by this data, which is still anecdotal [with] small numbers. However, there's efficacy data that seems to be coming out of this trial for [patients who are] rechallenged with checkpoint inhibitors following treating with this intralesional agent. Currently, this study is expanding to meet a higher accrual goal to give us additional data points to support this early efficacy signal [and] get some more immune correlates.

We're in talks to try to move it forward to a larger randomized registrational trial in MCC where we've seen the best signal so far. There's a lot of enthusiasm moving this forward to a bigger study that hopefully can be opened in the not too distant future.

What would you like colleagues to know about this treatment?

There's a nice early signal from this product, and I hope that this will be a supported trial in many of the major academic centers when we try to start the follow-up study. We encourage providers to think about this in their referrals to finish what we're starting.


Brohl AS, Markowitz J, Eroglu Z, et al. Phase 1b trial of IFx-Hu2.0, a novel personalized cancer vaccine, in checkpoint inhibitor resistant merkel cell carcinoma and cutaneous squamous cell carcinoma. J Clin Oncol. 2023;41(suppl 16):9534. doi:10.1200/JCO.2023.41.16_suppl.9534

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