Inclusion Criteria:
1. Have a histologically confirmed advanced melanoma stages III b/c or IV, with at least
the following superficial lesions: 5 lesions if diameter < 1 cm or 3 lesions if
diameter > 1 cm.
2. Could have received previous therapy included CT, antiCTLA4 or antiBRAF/antiMEK
treatment or be treatment naïve.
3. Be willing and able to provide written informed consent/assent for the trial.
4. Be >= 18 years of age on day of signing informed consent.
5. Have measurable disease based on RECIST 1.1.
6. Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
prior to initiation of treatment on Day 1. Subjects for whom newly-obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may submit an
archived specimen only upon agreement from the Sponsor.
7. Have a performance status ≤ 2 on the ECOG Performance Scale. (Ambulatory and capable
of all self-care but unable to carry out any work activities. Up and about more than
50% of waking hours.)
8. Demonstrate adequate organ function as defined in. 9. Have a baseline total body CT scan (brain MRI if brain metastasis are suspected)
1. Patients with brain metastasis are allowed to participate if previously treated
and brain lesion stability or inactivity is demonstrated. Patients with a history
of brain metastasis are required to have a pre-baseline brain MRI at least 60
days (2 months) before the Screening/Baseline visit (Visit 1) for comparison to
the Screening (Visit 1) MRI. Patients for whom MRI is contraindicated will
undergo head CT. Stable/inactive disease is determined by comparing the pre-
baseline and screening/baseline MRI/CT results.
2. Patients presenting with brain metastasis at Screening/Baseline who had no known
previous brain involvement and who had no brain MRI/CT tests at least 60 days (2
months) before Screening/Baseline are considered screening failures and will be
excluded from study enrollment.
10. Have cutaneous or subcutaneous metastases from melanoma that are accessible for the
application of electric pulses using the single use, sterile CLINIPORATOR™ electrodes
(5 lesions if diameter <1 cm or 3 lesions if diameter >1 cm). For patients presenting
with more than 7 lesions, the lesions with the largest diameters that fall within the
<10 to 30 mm size requirements will be considered "target" lesions for RECIST criteria
and study purposes. The others will be recorded and monitored but will not considered
as Target.
11. Have lesions clearly requiring palliative treatment [e.g., symptomatic (bleeding,
draining, painful), disfiguring or causing distress to the patient].
12. A treatment-free period of three
- (3) weeks before enrolling in the study.
NOTE:
Patients receiving concomitant treatments for unrelated existing pathologies are
eligible for enrollment.
13. Life expectancy > 3 months.
14. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.
15. Female subjects of childbearing potential (Section 5.7.2) must be willing to use an
adequate method of contraception as outlined in Section 5.7.2
- - Contraception, for the
course of the study through 120 days after the last dose of study medication.
Note:
Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.
16. Male subjects of childbearing potential (Section 5.7.1) must agree to use an adequate
method of contraception as outlined in Section 5.7.1- Contraception, starting with the
first dose of study therapy through 120 days after the last dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject.
Exclusion Criteria:
1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment or has any ongoing treatment for
melanoma or with any non-study anticancer therapy or immunosuppressive agent.
2. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment.
3. Has a known history of active TB (Bacillus Tuberculosis)
4. Hypersensitivity to pembrolizumab or any of its excipients or known allergies to
Bleomycin.
5. Has received a cumulative lifetime dose of Bleomycin exceeding 250 mg/m2. 6. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
7. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at
baseline) from adverse events due to a previously administered agent.
- - Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and
may qualify for the study.
- - Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting
therapy.
8. Patient has a history of a malignancy (other than the disease under treatment in the
study) within 5 years prior to first study drug administration. This should exclude
adequately treated Stage 1 or Stage 2 basal/squamous cell carcinoma of the skin,
carcinoma in situ of the cervix or breast, or other in situ cancers. Shorter intervals
can be considered after discussion with Merck.
9. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 14 days prior to trial treatment. This exception does not
include carcinomatous meningitis which is excluded regardless of clinical stability.
10. Has epilepsy.
11. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. with use of disease modifying agents, corticosteroids or immunosuppressive
drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.
12. Has a history of (no-infectious) pneumonitis that require steroids or current
pneumonitis.
13. Has an active infection requiring systemic therapy.
14. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the subject's
participation for the full duration of the trial, or is not in the best interest of
the subject to participate, in the opinion of the treating investigator.
15. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
16. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.
17. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
18. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
19. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
20. Has primary ocular melanoma. 21. Non-cutaneous/subcutaneous symptomatic or rapidly progressive metastases. 22. Cardiac arrhythmias [e.g., significant ventricular arrhythmia such as persistent
ventricular tachycardia and/or ventricular fibrillation; severe conduction disorders
as atrioventricular block 2 and 3, sinoatrial block]
23. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
