Trial Outcomes & Findings for Phase II Intratumoral IL12 Plasmid Electroporation in Cutaneous Lymphoma (NCT NCT01579318)

Participants were enrolled at 2 investigative sites in the United States from 08 June 2012 to 03 June 2014.

Phase II Intratumoral IL12 Plasmid Electroporation in Cutaneous Lymphoma

ORR is defined as the percentage of participants that achieved a complete response (CR) or partial response (PR) as assessed by mSWAT score. The mSWAT defines 3 lesion types and assigns each a weighing factor: patch (no induration or significant elevation)=1; plaque (induration, crusting, ulceration or poikiloderma)=2; tumor (solid or nodular ≥ 1 cm in diameter with evidence of deep infiltration and/or vertical growth)=4. Lesions are assessed by body surface area (BSA) where palm + fingers = approximately 1% BSA in each of 12 areas (head, neck, anterior trunk, arms, forearms, hands, posterior trunk, buttocks, thighs, legs, feet, groin), and the sum of each area of BSA is multiplied by its weighing factor. An overall sum of each subtotal represents the mSWAT score (0=no lesions; 400=lesions covering all areas). CR=100% clearance of skin lesions; PR= 50%-99% clearance of skin disease from baseline without new tumors ( ≥1.0 cm in diameter) in patients with T1, T2 or T4 only skin disease.

ORR is defined as the percentage of participants that achieved a complete response (CR) or partial response (PR) as assessed by mSWAT Composite Global Score. This assessment evaluated skin, lymph node, blood and visceral involvement. The response generated in each category was used to determine the Global ORR: CR=complete disappearance of all clinical evidence of disease or, no involvement of disease at baseline through time of response evaluation (NI); PR=regression of measurable disease as follows: 100% clearance of skin lesions, all other categories do not have CR/NI and no category has progressive disease (PD) -OR- 50%-99% clearance of skin disease from baseline without new tumors ( ≥1.0 cm in diameter) in patients with T1, T2 or T4 only skin disease, and if any other category was involved at baseline, at least one has CR/PR and no category has PD.

An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, medical treatment or procedure and which did not necessarily have to have had a causal relationship with this treatment. An adverse event could have, therefore, been any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, medical treatment or procedure whether or not considered related to the medicinal product. An SAE was defined an any untoward medical occurrence that at any dosage resulted in one or more of the following: death, A life-threatening adverse event (real risk of dying), inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability/incapacity, congenital anomaly, required intervention to prevent permanent impairment of damage.

Duration of overall objective response (CR or PR) is defined as the number of days from the initial documentation of an objective response to the most current evaluation of that response or to documentation of progression assessed by mSWAT Skin Score: CR=100% clearance of skin lesions; PR= 50%-99% clearance of skin disease from baseline without new tumors ( ≥1.0 cm in diameter) in patients with T1, T2 or T4 only skin disease.

Time to overall objective response (CR or PR) is the number of days from the start of therapy to the first documentation of objective response assessed by mSWAT Skin Score: CR=100% clearance of skin lesions; PR= 50%-99% clearance of skin disease from baseline without new tumors ( ≥1.0 cm in diameter) in patients with T1, T2 or T4 only skin disease.

Participants were to complete the following QoL assessments prior to clinical evaluations every 4 weeks: Skindex29, FACT-G (Functional Assessment of Cancer Therapy -General) and VAS-P (Visual Analog for Pruritus) questionnaires.

This outcome measure was erroneously entered as secondary but is truly an exploratory endpoint. Planned analyses were: 1. Transcriptional analysis of interferon pathway activation, antigen presentation and processing machinery (APM) upregulation, and immune cell infiltration in tissue at baseline and post-treatment. 2. Changes in the characterization of local tissue effects, proportion and phenotype, of intratumoral leukocyte subsets post-treatment. 3. Changes in T cell receptor clonal expansion and persistence of initial clones post- treatment. 4. Changes in FOXP3 methylation and quantification of regulatory T cells post- treatment.

This outcome measure was erroneously entered as secondary but is truly an exploratory endpoint. Planned analyses were: 1. Changes in the proportion of circulating regulatory and effector T cells in peripheral blood. 2. Changes in phenotype of leukocyte subsets and T cell receptor clonal expansion