Trial of pIL-12 Electroporation Malignant Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Tavokinogene Telseplasmid (tavo); OncoSec Medical System (OMS)
Intervention description: Patients received intratumoral injection(s) of tavo.; Electroporation via OMS was performed immediately following intratumoral injection of tavo. A sterile applicator containing 6 stainless steel electrodes arranged in a circle were placed around the tumor. The applicator was connected to the OMS power supply and six pulses were administered to each tumor lesion at the approximate point of tavo injection.
Intervention MeSH terms: Interleukin-12
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This study will assess the safety and effectiveness of different dosing regimens of
      ImmunoPulse IL-12® in malignant melanoma. ImmunoPulse IL-12® is the combination of
      intratumoral interleukin-12 gene (also known as tavokinogene telseplasmid [tavo]) and in vivo
      electroporation-mediated plasmid deoxyribonucleic acid [DNA] vaccine therapy (tavo-EP)
      administered using the OncoSec Medical System (OMS). ImmunoPulse IL-12® is a gene therapy
      approach to directly induce a pro-inflammatory response within a tumor to initiate and/or
      enhance anti-tumor immunity.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with advanced cutaneous or subcutaneous in-transit or metastatic melanoma
             (main and addendum)

          -  Age ≥ 18 years of age (main and addendum).

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (main and addendum).

          -  Patients may have had prior chemotherapy or immunotherapy (vaccines, interferon,
             ipilimumab, or IL-2) with progression or persistent disease. All chemotherapy or
             immunotherapy (prior therapies for cancer per the addendum) must have been stopped 4
             weeks prior to electroporation (main part) or prior to enrollment (addendum), unless
             the sponsor medical monitor approval was obtained.

          -  Patients may have had radiation therapy, but must have progressive disease after
             radiation therapy if the lesions to be treated are within the radiation field. Per the
             main study Protocol Amendment 10 (Version 11.0), dated 27 April 2016, all prior
             treatment toxicities had to be resolved to Grade 1. Per the study Addendum Amendment
             5, dated 27 April 2016, all prior chemotherapy or immunotherapy treatment-related
             adverse events (AEs) must have been resolved to baseline or Grade 1 at the time of
             study enrollment; and all prior radiation treatment AEs must have been resolved to
             baseline at the time of study enrollment.

          -  Had a minimum of 2 eligible tumors and could have had up to 4 eligible tumors treated
             with electroporation (main part).

          -  Must have had a lesion at baseline eligible for treatment, meeting all of the
             following criteria: at least 0.3 cm x 0.3 cm in longest perpendicular diameters; and
             accessible for electroporation (addendum).

          -  Must have had at least 1 additional lesion that could have been followed for distant
             regression and that met all of the following criteria: must have remained untreated
             for duration of the study; and had longest perpendicular diameters at least 0.3 cm x
             0.3 cm by clinical measurement; or at least 1.0 cm x 1.0 cm by computed tomography
             (CT) for non-nodal lesions; or at least 1.5 cm x 1.5 cm by CT for malignant lymph
             nodes (addendum).

          -  For women of childbearing potential, a negative serum or urine pregnancy test within
             14 days to the first study drug administration, and use of birth control from 30 days
             prior to the first day of study drug administration and 30 days following last day
             study drug administration was required. Male patients must have been surgically
             sterile, or must have agreed to use contraception during the study and at least 30
             days following the last day of study drug administration (addendum).

          -  Had a creatinine level < 2 x upper limit of normal (ULN), and serum bilirubin within
             institutional normal limits obtained within 4 weeks prior to enrollment (main part and
             addendum).

          -  Had aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 1.5 x ULN
             within 4 weeks prior to enrollment (addendum).

          -  Had an absolute neutrophil count (ANC) > 1000/mm and platelet count > 100,000 /mm
             within 4 weeks prior to registration (main part) or enrollment (addendum).

          -  Were able to give informed consent and to follow guidelines given in the study (main
             part and addendum).

        Exclusion Criteria:

          -  Prior therapy with IL-12 or prior gene therapy (main and addendum).

          -  Had an ECOG performance score of 3 or 4 (main part).

          -  Concurrent immunotherapy, chemotherapy, or radiation therapy for duration of patient
             participation on study (main part and addendum). For the study addendum, approved anti
             PD1 agents could have been permitted at the investigator's discretion and in
             consultation with the sponsor's medical monitor.

          -  Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess,
             etc.) at time of study entry (main part) or enrollment (study addendum).

          -  Pregnant or breast-feeding women (main part and addendum).

          -  Women of childbearing age must have had a negative pregnancy test and had to be
             willing to use a highly effective method of contraception. Men who were sexually
             active must also have been willing to use an accepted and effective method of
             contraception (main part).

          -  Patients with electronic pacemakers or defibrillators are excluded from this study
             (main part and addendum).

          -  The patient is known to be positive for Human Immunodeficiency Virus (HIV) or has
             another confirmed or suspected immunosuppressive or immunodeficient condition
             (patients with thyroiditis are eligible) (addendum).

          -  Life expectancy of less than 6 months (main part and addendum).

          -  Had significant disease or uncontrolled disease, ie, cardiovascular renal, hepatic,
             endocrine, metabolic, neurologic, or other significant disease that could have limited
             the patient's ability to participate in the study as determined by the investigator or
             medical monitor (main part).

          -  History of significant cardiovascular disease (i.e. New York Heart Association (NYHA)
             class 3 congestive heart failure; myocardial infarction with the past 6 months;
             unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or
             ventricular cardiac arrhythmias) (study addendum).

          -  Other clinically significant co-morbidities such as uncontrolled pulmonary disease,
             uncontrolled diabetes, active central nervous system (CNS) disease, active infection
             or any other condition that could compromise the patients participation in the study
             according to the investigator (study addendum).