Abstract CT241: Trial in progress: IFx-Hu2.0 (plasmid DNA coding for Emm55 streptococcal antigen in a cationic polymer) phase I first in human study for unresectable stage III or stage IV cutaneous melanoma
Authors: Markowitz Joseph , Brohl Andrew , Sarnaik Amod A. , Eroglu Zeynep , De Aquino Deanryan B. , Khushalani Nikhil , Tarhini Ahmad , Sondak Vernon K. , Pilon-Thomas Shari 
Published: September 2020

Abstract
Background: Anti-PD-1 and anti-CTLA4 immune-based therapeutics have vastly improved melanoma survival rates, but many patients still do not benefit from these therapies. IFx-Hu2.0 is a plasmid DNA encoding the streptococcal membrane protein, Emm55, contained within a cationic polymer. Preliminary correlative laboratory data from the first in human IFx-Hu2.0 phase I feasibility study for use as an intralesional melanoma therapy is reported. No clinical data will be presented. The melanoma tumor microenvironment, pre- and post-treatment, was analyzed on FFPE tissues collected from the first three patients with a panel consisting of CD3, CD8, FOXP3, PD1, PDL1, SOX10 and DAPI. The numbers of SOX10+ melanoma cells tended to decrease with treatment (Patient 1: 16.7% SOX10+ cells pre-treatment, 0.3% SOX10+ cells post treatment; Patient 2: 47.1% pre/6.0% post; Patient 3: 49.0% pre/52.7% post). Multi-parameter analysis revealed that when the numbers of SOX10+ cells decreased, there were an increased number of T cells in the tumor environment. This observation also held true for the whole section for patient 2. In this patient, there were 0.3% CD3+CD8+ T cells prior to treatment but this number increased to 15.2% after treatment. Interestingly, the numbers of FOXP3 regulatory T cells also increased in this patient suggesting the formation of an immune response. Taken together, IFx-Hu2.0 is proposed to create an immune response in melanoma patients and is being tested in a first in human trial. Methods: Up to six patients (&gt;18 years) with unresectable stage III or IV cutaneous melanoma will have cutaneous melanoma lesions injected with IFx-Hu2.0 to test the safety, tolerability, and feasibility of intralesional IFx-Hu2.0 injection. The subjects must have at least one lesion available for injection and another biopsiable lesion. This trial is unique as a cutaneous lesion as small as 3 mm may be injected. To be eligible, subjects should have been considered for anti-PD-1 therapy, TVEC and/or BRAF inhibition as indicated in the FDA labels for those agents. Small brain metastases (1 cm) are permitted assuming the subjects receive concurrent radiation at a site distant from intralesional injection with a greater than 3-month life expectancy. These patients may not be receiving any other systemic therapies, may not have uncontrolled hepatitis/HIV infection, and may not have a history of immunosuppression as is seen in patients who have undergone organ transplantation. For correlative studies, 4 tubes of peripheral blood will be collected at the beginning of the study and at the dose limiting toxicity (DLT) assessment visit 28 days later. Trial subjects will have the option of continued dosing every 3 weeks if they have a response to therapy. Success of the study is defined as being able to treat 5/6 subjects without DLT at 28 days. Three of the six planned trial subjects have been enrolled as of January 2020 (Clinical trial registry number: NCT03655756).
Citation Format: Joseph Markowitz, Andrew Brohl, Amod A. Sarnaik, Zeynep Eroglu, Deanryan B. De Aquino, Nikhil Khushalani, Ahmad Tarhini, Vernon K. Sondak, Shari Pilon-Thomas. Trial in progress: IFx-Hu2.0 (plasmid DNA coding for Emm55 streptococcal antigen in a cationic polymer) phase I first in human study for unresectable stage III or stage IV cutaneous melanoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT241.