This pilot study will evaluate the pharmacodynamic effects of intratumoral injection of
pIL-12 followed immediately by electroporation (IT-pIL12-EP). A minimum of ten patients
with biopsy-accessible triple negative breast cancer (TNBC) will be treated in this study.
Additional patients, up to a maximum of 25 patients, may be enrolled based upon
pharmacodynamic observations and at the discretion of the Principal Investigator, in
consultation with the Sponsor. All patients will receive a single 28-day treatment cycle.
One lesion will remain untreated (the control lesion). Treatment will be administered on
Days 1,5, and 8 of the single 28-day cycle. Treatments will consist of direct injection of
pIL-12 into tumor lesions, followed immediately by electroporation of the lesions. At the
end of the treatment cycle, patients will return to clinic for a final safety evaluation and
tumor biopsy. This end of study (EOS) visit will occur prior to initiating any new
All patients will undergo tumor biopsies at two separate timepoints for molecular and
histological analyses associated with the primary endpoint. At least one lesion will be
biopsied at Screening (pre-treatment sample). Biopsies of the untreated control lesion and
at least one treated lesion will be obtained at the EOS visit (post-treatment samples).
Additional tumor biopsy samples may be requested if there is either tumor regression or
progression prior to EOS.
Duration of participation will be approximately 4 weeks for each patient. A patient is
considered to have completed the study if all three IT-pIL12-EP treatments (Days 1, 5, & 8)
and all required pre- and post-treatment tumor biopsies have been obtained and EOS safety
follow-up evaluations have been performed.
- Histologically confirmed diagnosis of locally-advanced, inoperable, metastatic and/or
treatment-refractory triple negative breast cancer (TNBC). Patients must have both
ER and PR staining < 5% and be HER2-negative.
- Age 18 years.
- ECOG Performance Status of 0-1.
- Life expectancy 6 months.
- 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.
Radiation treatment must be completed 4 weeks prior to Cycle 1 Day 1.
- Adequate hepatic function with total bilirubin and ALT < 1.5X the upper limit of
normal (ULN), except in patients with Gilbert's Syndrome must have a total bilirubin
< 3X ULN and ALT < 3X ULN. In cases of known liver metastases, ALT 5X ULN is
acceptable (total bilirubin must be < 1.5X ULN).
- Adequate renal function, estimated or calculated creatinine clearance of > 50 mL/min
(calculated using the formula of Cockcroft and Gault) -or- serum creatinine 2.0
- Adequate hematological function, defined as ANC 1,500/mm3, Hb 9.0 g/dL, and
platelet count 100,000/mm3.
- Lesions that are accessible for injection and electroporation, defined as cutaneous
or subcutaneous disease.
- At least 2 anatomically distinct lesions accessible for biopsy.
- Must consent to study-specific biopsies at two separate timepoints: pre-treatment
(Screening) and post-treatment (Day 28 or EOS).
- Tumor lesions in the CNS are permitted but lesions must have been stable for at least
3 months prior to Cycle 1 Day 1 (C1D1). Stable CNS lesions are defined as not
requiring steroid prophylaxis or other medications to prevent seizures or other
complications associated with CNS lesions and no evidence of worsening of CNS
- Female patients of childbearing potential must have a negative serum or urine
pregnancy test within 3 days prior to C1D1 and agree to use dual methods of
contraception during the study and for a minimum of 30 days following the last
treatment. Post menopausal females (>45 years old and without menses for > 1 year)
and surgically sterilized females are exempt from these requirements.
Male patients must use an effective barrier method of contraception during the study and
for a minimum of 30 days following the last treatment if sexually active with a female of
- Resolution of all treatment-related toxicities, except alopecia, anemia and
neuropathy, from any previous cancer therapy to Grade 1 prior to the first dose of
- Ability to provide written informed consent.
- Any other current or previous malignancy within the past three years that, in the
opinion of the Principal Investigator, will interfere with study-specific objectives.
- Patients with electronic pacemakers or defibrillators.
- Chemotherapy or hormonal therapy for anti-cancer treatment within 28 days prior to
Cycle 1 Day 1.
- Immunotherapy or biological therapy (e.g., monoclonal antibodies) within 28 days
prior to Cycle 1 Day 1, unless pre-approval is obtained from the Sponsor Medical
- Treatment with unapproved investigational therapeutic agent within 28 days prior to
Cycle 1 Day 1, unless pre-approval is obtained from the Sponsor Medical Monitor.
- Patients receiving systemic steroid therapy for a chronic inflammatory condition
(e.g., rheumatoid arthritis, Crohn's Disease, etc.). Topical steroids are also
excluded. Nasal and inhaled steroids are permitted.
- Unstable/inadequate cardiac function:
- symptomatic ischemia
- uncontrolled or clinically significant conduction abnormalities; first degree AV
block or asymptomatic LAFB/RBBB are eligible
- myocardial infarction in the previous six months
- congestive heart failure (New York Heart Association class III to IV)
- Major surgery within 28 days prior to C1D1.
- Infection requiring parenteral antibiotics, antivirals, or antifungals within 2 weeks
prior to C1D1.
- Patients who are known to have HIV infection/seropositivity.
- Active Hepatitis A, B, or C infection or known to be positive for HCV RNA or HBV
surface antigen without vaccination.
- Serious psychiatric or medical conditions that could interfere with treatment or
- Patients who are pregnant or lactating.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both