Inclusion Criteria:
1. Written informed consent and HIPAA authorization for release of personal health
information prior to registration. NOTE: HIPAA authorization may be included in the
informed consent or obtained separately.
2. Male and female, age ≥ 18 years at the time of consent.
3. ECOG Performance Status of 0-1 within 28 days prior to registration.
4. Histological or cytological evidence of Merkel cell cancer per AJCC, 8th edition.
5. Presence of somatostatin receptors by Ga-68 dotatate (or equivalent) imaging, which
is a requirement for PRRT (lutetium Lu 177 dotatate [Lutathera®]). Must have at
least one measurable lesion per RECIST 1.1.
6. Must have progressed on treatment with an anti-PD-1/L1 mAb administered either as
monotherapy or in combination with other checkpoint inhibitors or other therapies.
PD-1 treatment progression is defined by meeting all of the following criteria:
- - Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
- - Has demonstrated disease progression after anti-PD-1/L1 as defined by RECIST
v1.1.
- - Progressive disease has been documented within 12 weeks from the last dose of
anti-PD-1/L1 mAb.
Note: This determination is made by the local investigator.
Once disease progression is confirmed, the initial date of disease progression
documentation will be considered the date of disease progression.
7. Prior cancer treatment must be completed and the subject must have recovered from
all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1
or baseline.
8. Demonstrate adequate organ function as defined in the table below. All screening
labs to be obtained within 28 days prior to registration.
- - Hematological:
- Absolute Neutrophil Count (ANC): ≥ 1500/uL.
- - Platelets: ≥100,000/uL.
- - Hemoglobin (Hgb): ≥9.0g/dL or ≥5.6mmol/L.
- - Renal:
- Creatinine: 1.5 x ULN OR.
- - Measured or calculated creatinine clearance (GFR can also be used in place
of creatinine or CrCl): ≥30mL/min for participant with creatinine levels
>1.5 x institutional ULN.
- - Hepatic:
---Total bilirubin: ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with
total bilirubin levels >1.5 x ULN.
- - AST(SGOT) and ALT(SGPT): ≤2.5 x ULN (≤5 x ULN for participants with liver
metastases)
- Coagulation:
- International normalized ratio (INR) OR prothrombin time (PT): ≤1.5 × ULN
unless participant is receiving anticoagulant therapy as long as PT or
aPTT is within therapeutic range of intended use of anticoagulants.
- - Activated partial thromboplastin time (aPTT): ≤1.5 × ULN unless
participant is receiving anticoagulant therapy as long as PT or aPTT is
within therapeutic range of intended use of anticoagulants.
9. Females of childbearing potential who are sexually active with a male able to father
a child must have a negative serum pregnancy test within 7 days prior to
registration.
10. Females of childbearing potential who are sexually active with a male able to father
a child must be willing to abstain from heterosexual activity or to use an effective
method(s) of contraception from the time of informed consent, during the study and
for 7 months after the last dose of study drug(s). Males able to father a child who
are sexually active with female of childbearing potential must be willing to abstain
from heterosexual activity or to use an effective method(s) of contraception from
initiation of treatment, during the study and for 120 days after the last dose of
study drug(s).
11. Participants who are HBsAg positive are eligible if they have received HBV
anti-viral therapy for at least 4 weeks and have undetectable HBV viral load prior
to registration.
Note: Participants should remain on anti-viral therapy throughout study intervention
and follow local guidelines for HBV anti-viral therapy post completion of study
intervention.
Hepatitis B screening tests are not required unless:
- - Known history of HBV infection.
- - As mandated by local health authority.
12. Participants with a history of HCV infection are eligible if HCV viral load is
undetectable at screening.
Note: Participants must have completed curative anti-viral therapy at least 4 weeks
prior to randomization.
Hepatitis C screening tests are not required unless:
- - Known history of HCV infection.
- - As mandated by local health authority.
13. HIV-infected participants must have well-controlled HIV on anti-retroviral therapy
(ART), defined as:
1. Participants on ART must have a CD4+ T-cell count ≥350 cells/mm3 at the time of
screening. 2. Participants on ART must have achieved and maintained virologic suppression
defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of
detection) using the locally available assay at the time of screening and for
at least 12 weeks before screening. 3. It is advised that participants must not have had any AIDS-defining
opportunistic infections within the past 12 months.
4. Participants on ART must have been on a stable regimen, without changes in
drugs or dose modification, for at least 4 weeks before study entry (Day 1) and
agree to continue ART throughout the study NOTE: HIV-infected participants with
a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease are
excluded.
14. As determined by the enrolling physician or protocol designee, ability of the
subject to understand and comply with study procedures for the entire length of the
study.
Exclusion Criteria.Subjects meeting any of the criteria below may not participate in the study:
1. Has known additional malignancy that is progressing or has required active treatment
within the past 3 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in
situ of the bladder, that have undergone potentially curative therapy are not
excluded. Patients with controlled CLL must be off all therapy for at least 6
months.
2. 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.
3. 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.
4. 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 registration.
5. Has had an allogeneic tissue/solid organ transplant.
6. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its
excipients.
7. 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 (e.g., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.
8. Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has active TB (Bacillus Tuberculosis) infection.
11. 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.
12. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
13. Is pregnant or breastfeeding or expecting to conceive or father children within the
projected duration of the study, starting with the screening visit through 7 months
(females) or 120 days (males) after the last dose of trial treatment. NOTE: breast
milk cannot be stored for future use while the mother is being treated on study.
14. Clinically significant cardiovascular disease or cardiac insufficiency (New York
Heart Association classes III-IV), cardiomyopathy, preexisting clinically
significant arrhythmia, acute myocardial infarction within 3 months of enrollment,
angina pectoris within 3 months of enrollment.
