| Eligibility |
Inclusion Criteria:
1. Subjects with histologically confirmed diagnosis of inoperable locally advanced or
metastatic TNBC.
2. The following prior cancer therapy requirements apply to specific cohorts:
1. For Cohort 1 only, subjects must have received at least 1 prior line of systemic
chemotherapy or immunotherapy that includes an approved regimen.
2. For Cohort 2 only, subjects has had no prior systemic therapy in the
advanced/metastatic setting and must not have progression or recurrence of
disease within 6 months after the last dose of systemic neoadjuvant or adjuvant
treatment, if applicable.
3. Subjects must have TNBC defined as estrogen (ER) receptor and progesterone (PR)
receptor staining <10% and human epidermal growth factor receptor 2 (HER2) - negative
defined as immunohistochemistry (IHC) 0 to 1+
4. For Cohort 2, the participant must meet each of the following criteria:
1. Has baseline PD-L1 negative disease (defined as Dako 22C3 assay CPS<10 [or
equivalent, per sponsor agreement]) with results provided prior to start of study
drug dosing: Historic results or new local PD-L1 testing from tissue collected
within 6 months and without intervening therapy prior to Cycle 1 Day 1
2. Can provide a separate core or punch tumor biopsy collected at screening or
archival tissue collected within 6 months (and without intervening therapy) prior
to Cycle 1 Day 1
3. Has at least one lesion suitable for biopsy on Cycle 2 Day 1 (preferably same
lesion from which the screening sample was collected).
5. Subjects must not have disease that, in the opinion of the Investigator, is considered
amenable to potentially curative treatment.
6. Age = 18 years of age of day of signing informed consent.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8. Life expectancy of at least 6 months.
9. Participant has measurable disease based on RECIST v1.1 and has at least one
identified lesion (target or non-target) that is accessible (up to 1.5 cm from the
skin surface) and in a safe location for intratumoral injection and electroporation.
10. Demonstrate adequate organ function. All screening laboratories should be performed
within 10 days of treatment initiation.
11. Female participant of childbearing potential must have a negative pregnancy test (for
serum or urine pregnancy test, within 72 hours or 24 hours, respectively, prior to
receiving the first study drug administration). If the urine test is positive or
cannot be confirmed as negative, a serum pregnancy test will be required.
12. Female participant of childbearing potential must be willing to use an adequate method
of contraception from the first day of study treatment (or 14 days prior to the
initiation of study treatment for oral contraception) and through at least 120 days
following the last day of study treatment.
13. Male participant is surgically sterile OR agrees to use an adequate method of
contraception when having sex with women of childbearing potential and refrains from
sperm donation during the study treatment period and at least 120 days following the
last day of study treatment.
14. Participant is able and willing to give informed consent and to follow study
instructions.
Exclusion Criteria:
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.
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