Inclusion Criteria:
1. Signed informed consent.
2. Subjects must be 18 years old or older.
3. ECOG performance status of 0 to 1.
4. Histologically confirmed diagnosis of MCC amenable for radical surgery as defined by
local or institutional surgical practices, based on multidisciplinary team assessment.
Subjects must have one of the following stages of disease:
1. Stage IIA
- - IIB- III (according to the AJCC staging system 8th edition)
2.
Local/Regional recurrent disease after primary surgery, as defined as total
disease burden ≥ 1 cm diameter amenable for a radical intent surgery. Note: nodal
disease without any known primary (in absence of a primary cutaneous site after a
complete diagnostic/staging work-up including chest/abdomen CT-scan, dermatologic
clinical examination and 18F-FDG-PET scan) can be enrolled and will be considered
as Stage
Able to provide archival FFPE tumor samples (if collected within three months from
study enrollment) or have a tumor amenable to pre-treatment biopsy. Excisional,
incisional, or core- needle samples are acceptable. Fine needle aspirates are not
allowed.
6. No prior systemic treatment or neoadjuvant radiation therapy.
7. Adequate bone marrow function characterized by the following at screening:
1. Platelets ≥ 100 × 109/L. 2. Absolute neutrophil count (ANC) ≥1.5 x 109/L. 3. Hemoglobin ≥ 9.0 g/dL. 8. Adequate renal function characterized by serum creatinine ≤ 1.5 × upper limit of
normal (ULN) OR calculated by Cockroft-Gault formula or directly measured creatinine
clearance ≥ 60 mL/min at screening for subject receiving cisplatin OR creatinine
clearance ≥ 50 mL/min at screening for subject receiving carboplatin.
9. Adequate hepatic function characterized by the following at screening:
1. Serum total bilirubin ≤ 1.5 × ULN and < 2 mg/dL. Note: Subjects with Serum total
bilirubin ≥ 1.5 × ULN and conjugated bilirubin ≤ ULN or < 40% of total bilirubin
are allowed.
2. AST (SGOT) and/or ALT (SGPT) <2.5 x UNL.
10. Men must agree to take appropriate precautions to avoid fathering children (with at
least 99% certainty) from screening through 6 months after the administration of study
treatment and must refrain from donating sperm during this period. Permitted methods
that are at least 99% effective in preventing pregnancy (see Appendix A) should be
communicated to the participants and their understanding confirmed.
11. Women of childbearing potential must have a negative serum pregnancy test at screening
and before the first dose on Day 1 and must agree to take appropriate precautions to
avoid pregnancy (with at least 99% certainty) from screening through 180 days after
the administration of any study drug. Permitted methods that are at least 99%
effective in preventing pregnancy should be communicated to the participants and their
understanding confirmed.
12. Women of non-childbearing potential (i.e. surgically sterile with a hysterectomy
and/or bilateral oophorectomy OR ≥ 12 months of amenorrhea and at least 50 years of
age) are eligible.
13. Willingness to comply with scheduled visits, treatment plan, laboratory tests and
other study procedures.
Exclusion Criteria:
1. Prior systemic therapy for MCC, including chemotherapy and prior PD-1 or
PD-L1-directed therapy.
2. Primary tumor or nodal metastasis fixed to the carotid artery, skull base or cervical
spine.
3. Treatment with anticancer drugs, radiation therapy or participation in another
interventional clinical study within 28 days before the first administration of study
drug.
4. Distant metastases at any site.
5. Any known additional malignancy that is progressing or requires active treatment, or
history of other malignancy within 2 years of study entry except for cured basal cell
or squamous cell carcinoma of the skin, superficial bladder cancer, prostate
intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or
indolent malignancy.
6. Impaired cardiovascular function or clinically significant cardiovascular diseases,
including any of the following:
1. History of acute myocardial infarction, acute coronary syndromes (including
unstable angina, coronary artery bypass graft [CABG], coronary angioplasty or
stenting) ≤ 6 months prior to start of study treatment;
2. Symptomatic congestive heart failure (i.e., Grade 2 or higher), history or
current evidence of clinically significant cardiac arrhythmia and/or conduction
abnormality ≤ 6 months prior to start of study treatment, except atrial
fibrillation and paroxysmal supraventricular tachycardia.
7. History of autoimmune disease including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome,
multiple sclerosis, vasculitis, or glomerulonephritis.
Note: Subjects with a history of autoimmune-related hypothyroidism on a stable dose of
thyroid replacement hormone may be eligible. Subjects with controlled type I diabetes
mellitus on a stable insulin regimen, vitiligo or psoriasis not requiring systemic
treatment may be eligible.
8. History of chronic conditions (i.e. COPD) requiring systemic immune-suppression in
excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or
equivalent).
9. Evidence of interstitial lung disease or active noninfectious pneumonitis.
10. History of organ transplant, including allogeneic stem cell transplantation.
11. History or current evidence of any condition, therapy or laboratory abnormality that
might interfere with the subject's participation to the study or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.
12. Know active hepatitis B [positive HBV surface antigen (HBsAg) result] or hepatitis C.
Patients with a past or resolved HBV infection (defined as the presence of hepatitis B
core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for
hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative
for HCV RNA. 13. Known uncontrolled HIV infection. HIV-positive patients are eligible if their CD4+
cell count amounts to 300 cells per μL or more; HIV viral load must be undetectable
per standard of care assay, and they have to be compliant with antiretroviral
treatment.
14. Active infections requiring systemic therapy, or systemic antibiotic use up to 10 days
before Cycle 1 Day 1.
15. Live vaccines within 28 days prior to and for a duration of 90 days after the
administration of study drug are forbidden.
Note: Examples of live vaccines include, but are not limited to, the following:
measles, mumps, rubella, chickenpox/zoster, yellow fever, rabies, Bacillus Calmette
Guérin, and typhoid vaccine. Seasonal influenza vaccines for injection are generally
killed virus vaccines and are allowed. COVID-19 vaccine is allowed, with an interval
of 2 days before and 2 days after the administration of study drugs;
16. Known hypersensitivity to platinum, etoposide or any of the excipients that cannot be
controlled with standard measures (eg, antihistamines, corticosteroids).
17. Known allergy or hypersensitivity to any component of the study drug formulation.
18. Subjects who lack the ability or are unlikely, in the opinion of the investigator, to
comply with the Protocol requirements.
19. Subjects who are pregnant or breastfeeding.
