Inclusion Criteria:
1. Male/female subjects with histologically confirmed diagnosis of MCC, who have not
received prior systemic treatment for their advanced or metastatic MCC, are at least
18 years of age on the day of signing informed consent, will be enrolled in this
study.
2. Male participants:
A male participant must agree to use a contraception as detailed in Appendix 3 of this
protocol during the treatment period and for at least 120 days, corresponding to time
needed to eliminate any study treatments (e.g. 5 terminal half-lives for pembrolizumab
and/or any active comparator/combination) plus an additional 90 days (a
spermatogenesis cycle) after the last dose of study treatment and refrain from
donating sperm during this period.
Female participants:
3. A female participant is eligible to participate if she is not pregnant (see Appendix
3), not breastfeeding, and at least one of the following conditions applies:
a. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR b. A
WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the
treatment period and for at least 120 days (corresponding to time needed to eliminate
any study treatments (pembrolizumab and/or any active comparator/combination) plus 30
days (a menstruation cycle) after the last dose of study treatment.
4. The participant (or legally acceptable representative if applicable) provides written
informed consent for the trial.
5. Unresectable and locally advanced, relapsed or metastatic MCC stage IIIB-IV according
to American Joint Committee on Cancer (AJCC) TNM Staging Classification for Merkel
Cell Carcinoma (8th ed. 2017)
6. No prior systemic treatment for metastic MCC. Subjects who received adjuvant or
neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at
least 12 months prior to the onset of metastatic disease.
7. Have a life expectancy of at least 3 months.
8. Have measurable disease based on RECIST 1.1. Lesions situated in a previously
irradiated area are considered measurable if progression has been demonstrated in such
lesions.
9. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy
of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE)
tissue blocks are preferred to slides. Newly obtained biopsies are preferred to
archived tissue.
10. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
Evaluation of ECOG is to be performed within 7 days prior to the first dose of study
intervention.
11. Have adequate organ function (protocol table 4)
Exclusion Criteria:
1. A WOCBP who has a positive urine pregnancy test within 72 hours prior to allocation
(see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
2. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with
an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4,
OX-40, CD137).
3. Has received prior systemic anti-cancer therapy.
4. Has received prior radiotherapy within 2 weeks of start of study intervention.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
5. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the
first dose of study drug. Administration of killed vaccines is allowed.
6. Is currently participating in or has participated in a study of an investigational
agent or has used an investigational device within 4 weeks prior to the first dose of
study intervention.
7. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy
(in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of study drug.
8. Has a known additional malignancy that is progressing or has required active treatment
within the past 2 years. Participants with basal cell carcinoma of the skin, squamous
cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer or
carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone
potentially curative therapy are not excluded.
9. Has known active CNS metastases and/or carcinomatous meningitis. Participants with
previously treated brain metastases may participate provided they are radiologically
stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging
(note that the repeat imaging should be performed during study screening), clinically
stable and without requirement of steroid treatment for at least 14 days prior to
first dose of study intervention.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
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 and is allowed.
12. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.
13. Has an active infection requiring systemic therapy.
14. Has a known history of Human Immunodeficiency Virus (HIV) infection.
15. Has a known history of active Hepatitis B (defined as HBV DNA is detected) or known
active Hepatitis C virus (defined as HCV RNA quantitative is detected) infection.
16. Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, or is not in the best interest of
the participant to participate, in the opinion of the treating investigator.
17. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
18. 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 trial treatment.
19. Has had an allogenic tissue/solid organ transplant.
