This is a phase II, single-arm study of combination therapy of avelumab, haNK, and N-803 in
patients with Merkel Cell Carcinoma who have progressed on or after checkpoint inhibitor
therapy as assessed by ORR. Patients must have progressed on or within six months of
completing treatment with either avelumab or pembrolizumab. Patients will received treatment
for a maximum of two years, with avelumab and haNK administered every two weeks, and N-803
administered every three weeks. Radiologic evaluation will occur every eight weeks during the
first year of treatment, and every twelve weeks during the second year of treatment.
Inclusion Criteria:
1. Age ≥ 18 years on day of signing informed consent.
2. Able to understand and provide a signed informed consent that fulfills the relevant
IRB or IEC guidelines.
3. Histologically-confirmed metastatic MCC that has progressed during treatment or within
6 months after completing treatment with single-agent avelumab or pembrolizumab
therapy, as per FDA indication.
4. ECOG performance status of 0 to 2.
5. Have at least 1 measurable lesion of ≥ 1.0 cm.
6. Must have a recent FFPE tumor biopsy specimen following the conclusion of the most
recent anticancer treatment and be willing to release the specimen for exploratory
tumor molecular profiling. If an historic specimen is not available, the subject must
be willing to undergo a biopsy during the screening period, if considered safe by the
Investigator. If safety concerns preclude collection of a biopsy during the screening
period, a tumor biopsy specimen collected prior to the conclusion of the most recent
anticancer treatment may be used.
7. Must be willing to provide blood samples for exploratory analyses.
8. Must be willing to provide a tumor biopsy specimen 8 weeks after the start of
treatment for exploratory analyses, if considered safe by the Investigator.
9. Ability to attend required study visits and return for adequate follow-up, as required
by this protocol.
10. Agreement to practice effective contraception for female subjects of child-bearing
potential and non-sterile males. Female subjects of child-bearing potential must agree
to use effective contraception for up to 1 year after completion of therapy, and
non-sterile male subjects must agree to use a condom for up to 4 months after
treatment. Effective contraception includes surgical sterilization (eg, vasectomy,
tubal ligation), two forms of barrier methods (eg, condom, diaphragm) used with
spermicide, intrauterine devices (IUDs), and abstinence.
Exclusion Criteria:
1. Serious uncontrolled concomitant disease that would contraindicate the use of the
investigational drug used in this study or that would put the subject at high risk for
treatment-related complications.
2. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, [subjects
with mild rheumatoid arthritis that aren't currently receiving treatment for their
disease are eligible for enrollment], Addison's disease, or autoimmune disease
associated with lymphoma).
3. History of organ transplant requiring immunosuppression.
4. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
colitis).
5. Inadequate organ function, evidenced by the following laboratory results:
1. ANC < 900 cells/mm3.
2. Platelet count < 75,000 cells/mm3
3. Total bilirubin greater than twice the ULN (unless the subject has documented
Gilbert's syndrome).
4. AST (SGOT) or ALT (SGPT) > 2.5 × ULN (> 5 × ULN in subjects with liver
metastases).
5. ALP levels > 2.5 × ULN (> 5 × ULN in subjects with liver metastases, or >10 × ULN
in subjects with bone metastases).
6. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
clinically significant (ie, active) cardiovascular disease, cerebrovascular
accident/stroke, or myocardial infarction within 6 months prior to first study
medication; unstable angina; congestive heart failure of New York Heart Association
grade 2 or higher; or serious cardiac arrhythmia requiring medication.
7. Dyspnea at rest due to complications of advanced malignancy or other disease requiring
continuous oxygen therapy.
8. Current chronic daily treatment (continuous for > 3 months) with systemic
corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
reaction or anaphylaxis in subjects who have known contrast allergies is allowed.
9. Known hypersensitivity to any component of the study medication(s), including
anaphylactic reaction to sulfur-containing medications.
10. Subjects taking any medication(s) (herbal or prescribed) known to have an adverse drug
reaction with any of the study medications.
11. Participation in an investigational drug study or history of receiving any
investigational treatment within 14 days prior to the start of treatment on this
study, except for testosterone-lowering therapy in men with prostate cancer.
12. Assessed by the Investigator to be unable or unwilling to comply with the requirements
of the protocol.
13. Concurrent participation in any interventional clinical trial.
14. Pregnant and nursing women.
