This phase II trial is evaluating a biological therapy (Tavokinogene Telseplasmid - delivered by electroporation), in combination with an immunotherapy drug (Pembrolizumab), in patients with advanced triple negative breast cancerA Phase 2, Open-Label Study of Intratumoral Tavokinogene Telseplasmid Plus Electroporation in Combination With Intravenous Pembrolizumab Therapy in Patients With Inoperable Locally Advanced or Metastatic Triple Negative Breast Cancer

Exclusion

1. Subject has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
2. Subject has a clinically active brain metastases or leptomeningeal metastases. Participant who has a previously treated brain metastases or untreated asymptomatic brain metastases ≤5 mm may participate provided that they are radiologically stable (ie, without evidence of progression based on imaging during study screening), clinically stable, and without requirement of steroid treatment for at least 14 days prior to the first dose of study treatment.
3. Subject has had an allogenic tissue/solid organ transplant.
4. Subjects with electronic pacemakers or defibrillators.
5. Subject who have a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
6. Subject has active hepatitis B (defined as HBsAg reactive) or active hepatitis C (defined as HCV RNA [qualitative] is detected). Note: Participant with a history of HBV or HCV controlled by ongoing viral suppression therapy is allowed.
7. Subject has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg/day of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Subject has an active autoimmune disease that required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs).

9. Subject has received a live-virus or live-attenuated vaccine within 30 days prior to the first dose of study treatment. Note: Administration of killed vaccines are allowed.

   Seasonal flu vaccines and COVID-19 vaccines that do not contain live virus (including attenuated vaccines) are permitted.

10. Subject has severe hypersensitivity (≥Grade 3) to pembrolizumab or other anti-PD-1 monoclonal antibody therapy and/or any of its excipients.
11. For Cohort 2 only, participant has severe hypersensitivity (≥Grade 3) to or expected intolerance of the protocol-specified chemotherapy options. Participant must be able to tolerate at least one of the trial approved chemotherapy options.
12. Subject has received transfusion of blood products (including platelets or red blood cells) or colony stimulating factors (including G-CSF, GM-CSF, or recombinant erythropoietin) within 2 weeks prior to qualifying screening labs.
13. Subject has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
14. Subject has a history of interstitial lung disease.
15. Subject has an active infection requiring systemic therapy.
16. Subject has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating Investigator.
17. Participant has not recovered (ie, ≤Grade 1 or at baseline) from adverse events (AEs) due to a previously administered agent.
18. Subject has received any systemic anti-cancer agent or other local anti-cancer immunotherapy within 14 days prior to the start of study treatment.
19. Subject has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
20. Subject is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.