IFx-Hu2.0 for the Treatment of Patients With Skin Cancer

Study Overview
=================
Brief Summary
-----------------
One hundred patients will receive IFx-Hu2.0 on an outpatient basis at a single time point in a single lesion. These patients will be assessed for any immediate adverse reactions and at Week 4 (Day 28+/-5 days) for any delayed adverse events..

Detailed Description
-----------------
This is a multi-site, open-label, interventional, prospective, phase 1 trial to assess safety and tolerability of IFx-Hu2.0 in patients with basal cell carcinoma, squamous cell carcinoma, or cutaneous melanoma. A total of approximately one hundred (100) male and/or female adult patients (greater than or equal to 18 years old), of any ethnicity and race, with at least one cutaneous melanoma, squamous cell carcinoma, or basal cell carcinoma lesion accessible for direct injection, who meet all inclusion and no exclusion criteria, will be eligible for enrollment and treatment with IFx-Hu2.0. Enrollees will receive IFx-Hu2.0 as a single intralesional injection at a single time point. The target dose will be 100 μg of plasmid DNA per lesion injected at a final dose volume of 200 μL per lesion. The injected lesion will be completely excised at the follow-up visit four weeks later and will be biopsied for confirmation of diagnosis and for the establishment of a pathological response baseline peripheral blood will be collected from these patients prior to treatment administration and at the follow-up visit four weeks later. These samples will be used to perform complete blood counts (CBC) and clinical chemistry tests. A urine sample will be obtained for urinalysis for protein and blood at the same frequency. Blood samples will be drawn for immune response evaluation as well.

Official Title
-----------------
Phase 1 Trial of IFx-Hu2.0 to Evaluate Safety in Patients With Skin Cancer

Conditions
-----------------
Cutaneous Squamous Cell Carcinoma, Basal Cell Carcinoma

Intervention / Treatment
-----------------
* Biological: IFx-Hu2.0


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Ability to receive intralesional injections Male or female, aged ≥ 18 years Histologically confirmed cutaneous squamous cell carcinoma, or basal cell carcinoma with accessible lesions (based on archival tissue or new tissue biopsy for histological confirmation) Life expectancy of at least 24 weeks at the time of screening Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 Must have measurable disease greater than 3 mm At least one injectable lesion Adequate organ function as defined below (Note: these screening laboratory tests must be obtained within two weeks prior to the baseline visit, Day 0): 10.1. Hemoglobin (Hb) >10 g/dL 10.2. Absolute Neutrophil Count (ANC) >1,500 cells/mcL 10.3. Platelet Count (PLT) >75,000/mcL 10.4. Prothrombin Time (PT) or International Normalized Ratio (INR) ≤1.5 times the institutional ULN unless patient is receiving anticoagulant therapy as long as PT or INR is within therapeutic range of the intended use of anticoagulants. 10.5. Activated Partial Thromboplastin Time (aPTT) ≤1.5 times the institutional ULN unless patient is receiving anticoagulant therapy as long as aPTT is within therapeutic range of the intended use of anticoagulants. 10.6. Serum Creatinine (SCr) ≤1.5 times the institutional ULN 10.7. Total Bilirubin ≤1.5 times the institutional ULN 10.8. Aspartate Aminotransferase (AST) ≤3 times the institutional ULN 10.9. Alanine Aminotransferase (ALT) ≤3 times the institutional ULN 10.10. Lactate Dehydrogenase (LDH) ≤2 times the institutional ULN 10.11. Alkaline Phosphatase (ALP) ≤2.5 times the institutional ULN 10.12. Gamma GT (GGT) ≤2.5 times the institutional ULN Lymphocyte count ≥500,000 cells/mL For females of reproductive potential: must have a negative urine or serum pregnancy test result within 24 hours prior to receiving IFx-Hu2.0; must use highly effective contraception (e.g.,licensed hormonal or barrier methods) for at least one month prior to screening and agreement to use such a method during study participation and for an additional 26 weeks after the end of study treatment For males of reproductive potential: use of barrier method or other methods to ensure effective contraception with partner Exclusion Criteria: Concurrent participation in any other clinical trial Inability to consent for self Lesions on scalp with bone erosions must not be selected as injection sites for IFx-Hu2.0 Life expectancy of fewer than 24 weeks at the time of screening Prior systemic anti-cancer treatment within three weeks from start of treatment (Day 0) Treatment with any investigational product within the three weeks preceding injection Concurrent chemotherapy or biological therapy. Concurrent radiotherapy is allowed as long as it is not the same site as the injected lesion. Current treatment with systemic immunosuppressive corticosteroid (greater than 10 mg of daily prednisone) doses or other immunosuppressants such as those needed for solid organ transplants. Medications needed to treat conditions such as reactive airway disease are not excluded. Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 26 weeks after the last dose of trial treatment Immunizations for encapsulated bacteria were not given for patients who have undergone a splenectomy Serious underlying medical or psychiatric conditions, active infections requiring the use of antimicrobial drugs, or active bleeding that would make the subject unsuitable or unable to participate in the study Active Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) or Hepatitis B/C. Patients with treated HIV/AIDS or Hepatitis B/C with no evidence of active infection may be enrolled History of organ allograft transplantation Presence of any uncontrolled and significant medical or psychiatric condition which would interfere with trial safety assessments

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IFx-Hu2.0 (plasmid DNA) 0.1 mg/lesion<br>One hundred (100) patients will receive 0.1 mg of IFx-Hu2.0 injected intratumorally in a single lesion at a single time point and be followed-up 28 days thereafter. | Biological: IFx-Hu2.0<br>* The investigational drug product IFx-Hu2.0 is composed of the drug substance pAc/emm55 (pDNA) complexed with the two excipients in vivo-jetPEI® (linear polyethylenimine), a transfection reagent, and dextrose, a pDNA/polyethylenimine complex stabilizer. Therapeutic Classification: Immunomodulatory Agent Route of Administration: Intralesional (i.e. injection of cutaneous, subcutaneous or lymph nodal lesions) Mechanism of Action: Injection of IFx-Hu2.0 into the lesion facilitates the expression of the immunogenic Emm55 protein by the tumor cells. Physiological Effect: Expression of the emm55 gene by the tumor cells triggers immune recognition of tumor-specific and -associated antigens which leads to innate and adaptive immune responses.<br>* Other names: pAc/emm55;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Adverse Events | Rate of Adverse Events reported per Common Terminology Criteria for Adverse Events (CTCAE) v5.0 | 28 days post injection | 
| Number of Patients who completed the trial | Number of Patients who completed the trial per protocol without major deviations | 28 days post injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Pathological Complete Response (pCR) | Rate of patients with complete absence of residual viable tumor in the treated tumor bed on histological assessment of fully excised lesion | Definitive surgery 4 weeks post treatment | 
| Rate of Major Pathological Response (mPR) | Rate of patients with ≤10% of residual viable tumor present in the treated tumor bed on histological assessment of fully excised lesion | Definitive surgery 4 weeks post treatment | 
| Rate of Partial Pathological Response (pPR) | Rate of patients with ≤50% of residual viable tumor present in the treated tumor bed on histological assessment of fully excised lesion | Definitive surgery 4 weeks post treatment | 
| Rate of Pathological Non-Response (pNR) | Rate of patients with >50% of residual viable tumor present in the treated tumor bed on histological assessment of fully excised lesion | Definitive surgery 4 weeks post treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
BCC, cSCC, pAc/emm55, IFx-Hu2.0, Gene Therapy, Immunotherapy, Oncology, Immunology, plasmid DNA