Electroporation systems, methods, and apparatus

A method of treating a lesion at a lung of a subject who is non-responsive or predicted to be non-responsive to anti-PD-1 or anti-PD-L1 therapy, the method comprising:

• administering to the lesion an effective dose of at least one plasmid coding for IL-12;
• administering electroporation therapy to the lesion;
• and
• administering to the subject an effective dose of at least one checkpoint inhibitor;
• wherein administering the electroporation therapy comprises administering an electric pulse to the lesion using an electroporation system comprising:
• an applicator comprising:
• a plurality of electrodes comprising a first electrode having a first tip and a second electrode having a second tip, wherein the plurality electrodes are configured to move between a retracted position and a deployed position;
• wherein a distance between the first tip of the first electrode and the second tip of the second electrode is greater in the deployed position than in the retracted position;
• and
• a generator electrically connected to the plurality of electrodes,
• wherein administering the electric pulse to the lesion comprises disposing the first electrode and the second electrode into or adjacent to the lesion, and delivering the electric pulse from the generator to the first electrode and the second electrode.