Phase 1b trial of IFx-Hu2.0, a novel personalized cancer vaccine, in checkpoint inhibitor resistant merkel cell carcinoma and cutaneous squamous cell carcinoma.
Authors: Brohl Andrew Scott , Markowitz Joseph , Eroglu Zeynep , Silk Ann W. , Hyngstrom John Robert , Khushalani Nikhil I. , Tarhini Ahmad A. , De-Aquino Deanryan B. , Abraham Edith , Tsai Kenneth Yee , Thomas Jacob Stephen 
Published: June 2023

9534 Background: Merkel cell carcinoma (MCC) and cutaneous squamous cell carcinoma (cSCC) exhibit high response rate to immune checkpoint inhibitor (ICI) therapy. However, patients with advanced disease who fail initial ICI therapy have limited treatment options. IFx-Hu2.0 (IFx) is a plasmid DNA encoding for an immunogenic bacterial protein, Emm55, formulated with a transfection agent for direct intratumoral injection. In a phase 1 study in advanced melanoma, biomarker analyses demonstrated robust immune priming effects of IFx administration. As part of an ongoing Phase 1b study, we evaluated the safety and immunologic response of different schedules of IFx intratumoral administration in patients with advanced MCC or cSCC. We report the initial results of the first stage of this study. Methods: In the first trial stage (n = 9), IFx was administered intratumorally in up to 3 lesions on 3 schedules; weekly x 1, 2, or 3. We report safety data for these patients. Given the proposed potential for immune priming effects of IFx, we performed an unplanned exploratory analysis of post-protocol treatment efficacy to evaluate for response to ICI rechallenge if given. Results: Five patients with advanced MCC and four with cSCC were enrolled. Prior to trial enrollment, all patients with MCC received ICI with pembrolizumab (4) or avelumab (1), all had progressive disease with median 3 months treatment (2.0-4.5mo). All 4 patients with cSCC previously received cemiplimab with median 6 months treatment (3.0-11.5mo). IFx was well tolerated at all dose schedules evaluated with no treatment-related G3-5 adverse events observed. Best response to trial therapy was SD in 2 patients and PD in seven. One MCC patient experienced complete clinical response in 2 injected lesions, but progression of disease overall with development of new disease areas. Following completion of protocol therapy, all 5 MCC patients and 2 of 4 cSCC patients were treated with anti-PD(L)1 therapy as the immediate post-protocol therapy: pembrolizumab (3) or avelumab (2) in MCC and cemiplimab (2) in cSCC. Four of 5 MCC patients and 1 of 2 cSCC patients, or 5 of 7 total (71%), experienced objective response to ICI rechallenge in this setting, with duration of response ongoing in 4 patients (7+, 8+, 9+, 20+ months) and one response lasting 23 months. Conclusions: IFx-Hu2.0 is safe and well tolerated at weekly dosing repeated up to 3 weeks. An exploratory analysis showed that five of seven patients (71%) treated with standard of care ICI agents following protocol therapy experienced a durable objective response despite prior failure of this same drug class prior to protocol enrollment. An additional 11 patients are planned for enrollment in the expansion stage of the study using the weekly x3 dosing schedule. Preliminary biomarker analyses from the first nine patients are ongoing and will be presented. Clinical trial information: NCT04160065 .