A Phase II, Open-Label, Single-Arm Trial Using KEYTRUDA (Pembrolizumab) as Initial Systemic Therapy in the Treatment of Advanced Mycosis Fungoides
Phase: PHASE2
Conditions: Mycosis Fungoides, Sezary Syndrome, Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage II Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage III Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IV Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IVA1 Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IVA2 Mycosis Fungoides and Sezary Syndrome AJCC v8, Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v8
Sponsor: Mayo Clinic

Protocol Version: 30NOV2022 
 
MC1788 
 
 
Mayo Clinic Cancer Center 
 
A Phase II, Open-label, Single-Arm trial Using KEYTRUDA (pembrolizumab) as Initial Systemic 
Therapy in the Treatment of Advanced Mycosis Fungoides 
 
Sponsor/Principal Investigator: 
 
 
 
Co-Investigators: 
 
 
Statistician: 
  
FDA IND #: 
139381 
 
 
Trial Supported by: 
Funding: Merck & Co. 
 
 
Drug Availability: 
Drug Company Supplied: Pembrolizumab 
 
 
√Study contributor(s) not responsible for patient care 
 
 
 
 
Document History 
(Effective Date) 
Activation 
Amendment 1 
Amendment 2 
Amendment 3 
    Amendment 4 
     Amendment 5 
     Amendment 6 
December 20, 2018 
June 23, 2020 
October 30, 2020 
October 22, 2021 
June 22, 2022 
August 26, 2022 
Pending 

Protocol Version: 30NOV2022 
 
 

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Protocol Resources 
 
Questions: 
Contact Name: 
Patient eligibility*, test schedule, 
treatment delays/interruptions/adjustments, 
dose modifications, adverse events, 
forms completion and submission 
 
 
Forms completion and submission 
 
 
 
Protocol document, consent form, 
regulatory issues 
 
  
 
Non-paraffin biospecimens 
 
Serious Adverse Event Reporting 
 
 
*No waivers of eligibility allowed 

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Table of Contents 
 
A Phase II, Open-label, Single-Arm trial Using KEYTRUDA (pembrolizumab) as Initial Systemic 
Therapy in the Treatment of Advanced Mycosis Fungoides .......................................................................... 
Protocol Resources ........................................................................................................................................ 2 
Table of Contents .......................................................................................................................................... 3 
Schema .......................................................................................................................................................... 4 
1.0 
Background ................................................................................................................................... 6 
2.0 
Goals ........................................................................................................................................... 11 
3.0 
Registration Patient Eligibility .................................................................................................... 12 
4.0 
Test Schedule .............................................................................................................................. 15 
5.0 
Stratification Factors OR Grouping Factor .................................................................................. 17 
6.0 
Registration Procedures ............................................................................................................... 17 
7.0 
Protocol Treatment ...................................................................................................................... 19 
8.0 
Dosage Modification Based on Adverse Events .......................................................................... 19 
9.0 
Ancillary Treatment/Supportive Care .......................................................................................... 23 
10.0 
Adverse Event (AE) Monitoring and Reporting .......................................................................... 29 
11.0 
Treatment Evaluation/Measurement of Effect ............................................................................. 42 
12.0 
Descriptive Factors ...................................................................................................................... 45 
13.0 
Treatment/Follow–up Decision at Evaluation of Patient ............................................................. 45 
14.0 
Body Fluid Biospecimens ............................................................................................................ 48 
15.0 
Drug Information ......................................................................................................................... 49 
16.0 
Statistical Considerations and Methodology ............................................................................... 54 
17.0 
Pathology Considerations/Tissue Biospecimens ......................................................................... 58 
18.0 
Records and Data Collection Procedures..................................................................................... 60 
19.0 
Budget ......................................................................................................................................... 61 
20.0 
References ................................................................................................................................... 62 
Appendix I 
ECOG Performance Status ................................................................................................ 63 

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Schema 
 
 
 
 
Registration 
 
 
↓ 
 
 
Treatment Cycle 1 
IV Pembrolizumab: Day 1 
 
 
↓ 
3 Weeks1 
↓ 
 
 
Assess Clinical Response 
 
 
Responder 
(*CR, CR90, & PR, SD) 
 
 
*Continue Pembrolizumab Day 1 
 
 
 
 
 
Events at any time: 
CR 
Disease Progression 
Intolerable adverse effects 
Patient Refusal 
↓ 
 
 
Cycle = 21 days 
Window for all visits = ± 3 days 
1Patients who go off protocol treatment during Cycle 1 for reasons other than PD or CR, will 
continue to Survival follow-up. 
*The maximum duration of therapy is 24 months. If the patient achieves CR during this period, further , 
pembrolizumab cycles will be discontinued and the patient will proceed to survival followup. 
Survival Follow-up 
Clinical Follow-up: 30 & 90 days 
after EOT 
Non-Responder 
(mSWAT increase by 25%, 
alternative treatment 
OR 
Progressive, nodal, visceral, or blood 
disease**) 
Exit Study (No 
Follow-up) 

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**Non-responders include patients with progressive, nodal, visceral, or blood disease as assessed by 
repeat staging after Cycle 4 and at the end of treatment visit. 
 
Generic name: pembrolizumab, MK-3475 
Brand name(s): Keytruda™ 
Mayo Abbreviation: MK3475 
Availability: Mayo Clinic Pharmacy 

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1.0 
Background 
Mycosis fungoides (MF) is an incurable extranodal, T-cell non-Hodgkin lymphoma that 
accounts for 80% of all primary cutaneous lymphomas. Affected individuals initially 
develop pruritic patches initially in sun protected anatomic sites. Most presentations are 
indolent but 20% progress in a stepwise fashion from patch disease to raised plaque and 
nodular skin lesions with variable degrees of lymph node, blood, and visceral organ 
involvement (Wilcox, 2017). 
 
Patients who fail skin directed therapies receive systemic therapy with bexarotene, 
interferon, extracorporeal photopheresis, deacetylase inhibitors, methotrexate, 
pralatexate, gemcitabine, pegylated liposomal doxorubicin, bortezomib, and denileukin 
diftitox (Devata et al., 2016; Trautinger, 2017). These agents may be combined after the 
failure of monotherapy or rotated therapeutically if toxicity or efficacy limits use. 
 
Patients with advanced stage disease have a 5-year survival of 17-40%, and ultimately die 
of lymphoma and infectious complications associated with disease progression after 2-3 
lines of systemic therapy. 
 
Pembrolizumab, an immune checkpoint inhibitor of PD-1, has been recently reported to 
have clinical activity in MF previously treated with one systemic agent and also in 
patients with Sézary syndrome (SS) (Khodadoust et al., 2016). 
 
Pembrolizumab is presently FDA approved for the treatment of unresectable or 
metastatic melanoma, as first-line treatment of patients with metastatic non-small cell 
lung cancer (NSCLC) with high PD-L1 expression, recurrent or metastatic head and neck 
squamous cell carcinoma (HNSCC) with disease progression, and in refractory classical 
Hodgkin lymphoma (cHL) who have relapsed after three or more prior lines of therapy. 
 
1.1 
Pharmaceutical and Therapeutic Background 
 
The importance of intact immune surveillance in controlling outgrowth of 
neoplastic transformation has been known for decades. Accumulating evidence 
shows a correlation between tumor-infiltrating lymphocytes (TILs) in cancer 
tissue and favorable prognosis in various malignancies. In particular, the presence 
of CD8+ T-cells and the ratio of CD8+ effector T-cells / FoxP3+ regulatory T- 
cells seems to correlate with improved prognosis and long-term survival in many 
solid tumors. 
 
The PD-1 receptor-ligand interaction is a major pathway hijacked by tumors to 
suppress immune control. The normal function of PD-1, expressed on the cell 
surface of activated T-cells under healthy conditions, is to down-modulate 
unwanted or excessive immune responses, including autoimmune reactions. PD-1 
(encoded by the gene Pdcd1) is an Ig superfamily member related to CD28 and 
CTLA-4 which has been shown to negatively regulate antigen receptor signaling 
upon engagement of its ligands (PD-L1 and/or PD-L2). 

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The structure of murine PD-1 has been resolved. PD-1 and family members are 
type I transmembrane glycoproteins containing an Ig Variable-type (V-type) 
domain responsible for ligand binding and a cytoplasmic tail which is responsible 
for the binding of signaling molecules. The cytoplasmic tail of PD-1 contains 2 
tyrosine-based signaling motifs, an immunoreceptor tyrosine-based inhibition 
motif (ITIM) and an immunoreceptor tyrosinebased switch motif (ITSM). 
 
Following T-cell stimulation, PD-1 recruits the tyrosine phosphatases SHP-1 and 
SHP-2 to the ITSM motif within its cytoplasmic tail, leading to the 
dephosphorylation of effector molecules such as CD3ζ, PKCθ and ZAP70 which 
are involved in the CD3 T-cell signaling cascade. The mechanism by which PD-1 
down modulates T-cell responses is similar to, but distinct from that of CTLA-4 
as both molecules regulate an overlapping set of signaling proteins. PD-1 was 
shown to be expressed on activated lymphocytes including peripheral CD4+ and 
CD8+ T-cells, B-cells, T regs and Natural Killer cells. Expression has also been 
shown during thymic development on CD4-CD8- (double negative) T-cells as 
well as subsets of macrophages and dendritic cells. The ligands for PD-1 (PD-L1 
and PD-L2) are constitutively expressed or can be induced in a variety of cell 
types, including non-hematopoietic tissues as well as in various tumors. Both 
ligands are type I transmembrane receptors containing both IgV- and IgC-like 
domains in the extracellular region and contain short cytoplasmic regions with no 
known signaling motifs. 
 
Binding of either PD-1 ligand to PD-1 inhibits T-cell activation triggered through 
the T-cell receptor. PD-L1 is expressed at low levels on various non- 
hematopoietic tissues, most notably on vascular endothelium, whereas PD-L2 
protein is only detectably expressed on antigen-presenting cells found in 
lymphoid tissue or chronic inflammatory environments. 
 
PD-L2 is thought to control immune T-cell activation in lymphoid organs, 
whereas PD-L1 serves to dampen unwarranted T-cell function in peripheral 
tissues. Although healthy organs express little (if any) PD-L1, a variety of cancers 
were demonstrated to express abundant levels of this T-cell inhibitor. PD-1 has 
been suggested to regulate tumor-specific T-cell expansion in subjects with 
melanoma (MEL). This suggests that the PD-1/PD-L1 pathway plays a critical 
role in tumor immune evasion and should be considered as an attractive target 
for therapeutic intervention. 
 
Pembrolizumab is a potent and highly selective humanized monoclonal antibody 
(mAb) of the IgG4/kappa isotype designed to directly block the interaction 
between PD-1 and its ligands, PD-L1 and PD-L2. KeytrudaTM (pembrolizumab) 
has recently been approved in the United Stated for the treatment of patients with 
unresectable or metastatic melanoma and disease progression following 
ipilumumab and, if BRAF V600 mutation positive, a BRAF inhibitor. 
 
1.2 
Rationale 

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1.21 
Rationale for the Trial and Selected Subject Population 
There is no evidence-based algorithm for the treatment of MF, but therapies have 
been conventionally divided into skin-directed therapy and systemic therapy. 
Patients with early stage disease (patch/plaque disease without nodal or visceral 
involvement) are treated with topical corticosteroids, topical cytostatic agents, 
topical retinoids, superficial radiotherapy, and phototherapy. These modalities 
are rarely remittive but may temporarily clear involved skin and improve 
pruritus. 
 
For progressive early stage MF, high risk early-stage MF (thick plaques or 
follicular involvement), advanced-stage MF (presence of tumors, nodal 
involvement, erythroderma, visceral involvement), or SS, systemic therapy is the 
standard of care. Biologic response modifying agents such as IFN-alpha, 
bexarotene, or HDAC inhibitors are considered first line, as systemic multi-agent 
chemotherapy provides no survival advantage. 
 
However, the optimal treatment sequence is unknown and there is no clear 
evidence that sequential or step-wise combination systemic therapy is more 
efficacious or contributes to long-term survival or cure. Early/initial use of 
pembrolizumab in the treatment of advanced MF is postulated to have a unique 
therapeutic synergy, whereby the direct reduction of tumor burden by 
pembrolizumab further enhances the baseline endogenous host anti-tumor 
response that is subsequently amplified with additional scheduled treatments. 
This rationale supports the use of pembrolizumab as initial first line systemic 
therapy, as the endogenous anti-tumor host response is more robust earlier in the 
disease course and is thus more likely to produce clinical clearance of lesional 
skin. 
 
1.22 
Rationale for Dose Selection, Regimen, and Modification 
Multiple prior studies have been conducted to evaluate the safety and clinical 
activity of single agent pembrolizumab. The dose escalation portion of this trial 
evaluated three dose levels, 1 mg/kg, 3 mg/kg, and 10 mg/kg, administered every 
2 weeks (Q2W) in subjects with advanced solid tumors. All three dose levels 
were well tolerated and no dose limiting toxicities were observed.. Recent data 
from other clinical studies within the pembrolizumab program has shown that a 
lower dose of pembrolizumab and a less frequent schedule may be sufficient for 
target engagement and clinical activity. 
 
PK data analysis of pembrolizumab administered Q2W and Q3W showed slow 
systemic clearance, limited volume of distribution, and a long half-life (refer to 
IB). Pharmacodynamic data (IL-2 release assay) suggested that peripheral target 
engagement is durable (>21 days). This early PK and pharmacodynamics data 
provides scientific rationale for testing a Q2W and Q3W dosing schedule. 
 
A population pharmacokinetic analysis has been performed using serum 
concentration time data from 476 patients. Within the resulting population PK 
model, clearance and volume parameters of pembrolizumab were found to be 
dependent on body weight. The relationship between clearance and body weight, 
with an allometric exponent of 0.59, is within the range observed for other 
antibodies and would support both body weight normalized dosing or a fixed 
dose across all body weights. pembrolizumab has been found to have a wide 

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therapeutic range based on the melanoma indication. The differences in exposure 
for a 200 mg fixed dose regimen relative to a 2 mg/kg Q3W body weight based 
regimen are anticipated to remain well within the established exposure margins 
of 0.5 – 5.0 for pembrolizumab in the melanoma indication. The exposure 
margins are based on the notion of similar efficacy and safety in melanoma at 10 
mg/kg Q3W vs. the proposed dose regimen of 2 mg/kg Q3W (i.e. 5-fold higher 
dose and exposure). The population PK evaluation revealed that there was no 
significant impact of tumor burden on exposure. In addition, exposure was 
similar between the NSCLC and melanoma indications. Therefore, there are no 
anticipated changes in exposure between different indication settings. 
 
The rationale for further exploration of 2 mg/kg and comparable doses of 
pembrolizumab in solid tumors is based on: 1) similar efficacy and safety of 
pembrolizumab when dosed at either 2 mg/kg or 10 mg/kg Q3W in melanoma 
patients, 2) the flat exposure-response relationships of pembrolizumab for both 
efficacy and safety in the dose ranges of 2 mg/kg Q3W to 10 mg/kg Q3W, 3) the 
lack of effect of tumor burden or indication on distribution behavior of 
pembrolizumab (as assessed by the population PK model) and 4) the assumption 
that the dynamics of pembrolizumab target engagement will not vary 
meaningfully with tumor type. 
 
The choice of the 200 mg Q3W as an appropriate dose for the switch to fixed 
dosing is based on simulations performed using the population PK model of 
pembrolizumab showing that the fixed dose of 200 mg every 3 weeks will 
provide exposures that 1) are optimally consistent with those obtained with the 2 
mg/kg dose every 3 weeks, 2) will maintain individual patient exposures in the 
exposure range established in melanoma as associated with maximal efficacy 
response and 3) will maintain individual patients exposure in the exposure range 
established in melanoma that are well tolerated and safe. 
 
A fixed dose regimen will simplify the dosing regimen to be more convenient for 
physicians and to reduce potential for dosing errors. A fixed dosing scheme will 
also reduce complexity in the logistical chain at treatment facilities and reduce 
wastage. 
 
1.23 
Rationale for Endpoints 
The proposed primary and secondary efficacy endpoints conform to 
recommended consensus definitions of the International Society for Cutaneous 
Lymphomas (ISCL), the United States Cutaneous Lymphoma Consortium 
(USCLC), and the Cutaneous Lymphoma Task Force of the European 
Organization for Research and Treatment of Cancer (EORTC) and will permit a 
relative comparison to other published work using these definitions. 
 
The Primary efficacy endpoint will be the overall cutaneous response rate at 
week 27 by the Modified Skin Severity Assessment (mSWAT) score. 
 
The mSWAT is calculated using body surface area (BSA) of each MF lesion 
(palm plus fingers of the patient ≈ 1% BSA) in each of 12 areas of the body, 
multiplying the sum of the BSA of each lesion type by a weighting factor 
(patch=1, plaque=2, and tumor =4) and generating a sum of the subtotals of each 
lesion subtype. 

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Hypothesis: Biopsies in MF reveal an abnormal accumulation of clonal CD4+ 
helper T-cells initially in the epidermis and later in the dermis and subcutis. 
There is also a characteristic anti-tumor host response of infiltrating CD8+/TIA- 
1+ cytotoxic T-lymphocytes in lesional skin. Histologically, the intensity of this 
infiltrate diminishes with disease progression from patch, plaque to tumor disease 
and has been postulated to reflect the suppressive effects of TH2 cytokine 
production and CD25+ TReg phenotypic induction by the malignant CD4+ T- 
cells (Phillips et al., 2016; Rozati et al., 2016). 
 
Pembrolizumab is a humanized monoclonal IgG4 antibody directed against the 
receptor PD-1 (programmed cell death-1) expressed on the surface of activated T 
cells (Nguyen et al., 2017; Warren et al., 2017). 
 
We hypothesize PD-1 inhibition will preserve and enhance the anti-tumor 
responses in MF through effector T cell activation and TReg inhibition. (Wang et 
al., 2018) 
We have also conducted a preliminary analysis of PD-1/CD279 expression in a 
representative group of patch, plaque, and tumor MF biopsy specimens and 
found expression in nearly all cases; this finding further supports the hypothesis 
that pembrolizumab may have value in the management of all stages of MF. 
 
1.3 
Correlative Research 
 
1.31 
This study proposes to characterize the histologic features of the anti-tumor host 
response before and after treatment with pembrolizumab. Prior to the initial dose 
of pembrolizumab, a 6 mm punch skin biopsy of the most common presenting 
morphology (i.e. patch, plaque, or tumor) will be obtained for each study 
participant; at the second cycle (week 6), an additional 6 mm punch skin biopsy 
of the same morphologic type will be obtained. Immunohistochemistry will then 
be used to assess the levels of CD4, CD8, PD-1/CD279, and PD-L1 expression 
before and after treatment with pembrolizumab. 

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2.0 
Goals 
2.1 
Primary Goal 
To evaluate the antitumor activity of pembrolizumab in patients with advanced MF as 
initial systemic therapy. 
2.2 
Secondary Goals 
2.21 
To evaluate safety of pembrolizumab in this patient population. 
2.22 
To evaluate response rates of pembrolizumab in this patient population. 
2.23 
To determine the progression free survival, duration of response, time to 
response and overall survival of pembrolizumab in this patient population . 
2.3 
Correlative Research 
To characterize the histologic features of the anti-tumor response in patients with 
advanced MF before and after treatment with pembrolizumab. 

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3.0 
Registration Patient Eligibility 
3.1 
Registration – Inclusion Criteria 
3.11 
Age ≥ 
18 
years. 
3.12 
Histological confirmation of one of the following: 
• 
Stage IIB-IV Mycosis Fungoides not previously treated with systemic 
therapy 
• 
Stage IB/IIA Mycosis Fungoides with mSWAT ≥ 20 with high risk 
morphologic features defined as thick plaque disease and/or follicular 
involvement who have failed one form of skin-directed therapy. 
• 
Sézary Syndrome patients not previously treated with systemic therapy. 
3.13 
Measurable disease based on mSWAT and/or RECIST 1.1 (see Section 11.0). 
3.14 
Be willing to provide tissue from a newly obtained core or excisional biopsy of a 
tumor lesion. Note: Newly-obtained is defined as a specimen obtained up to 6 
weeks (42 days) prior to registration. Exception: 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. 
3.15 
ECOG Performance Status (PS)0 or 1 (Appendix I). 
3.16 
The following laboratory values obtained ≤28 days prior to registration. 
• 
Absolute neutrophil count (ANC) ≥1,500 /mcL 
• 
Platelet count ≥100,000/mcL 
• 
Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L without transfusion or EPO 
dependency (within 7 days of assessment) 
• 
Serum total bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects 
with total bilirubin levels > 1.5 ULN 
• 
Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 2.5 X 
ULN OR ≤ 5 X ULN for subjects with liver metastases 
• 
Albumin >2.5 mg/dL 
• 
Serum creatinine <=1.5 x upper limit of normal (ULN) OR Measured or 
calculated creatinine clearance >=60 ml/min for subject with creatinine levels 
>1.5 x institutional ULN. 
• 
PT/INR and PTT ≤1.5 X ULN OR if patient is receiving anticoagulant 
therapy and PT/INR or PTT is within therapeutic range of intended use of 
coagulants 
3.17 
Negative urine or serum pregnancy test done ≤ 28 days prior to registration and ≤ 
72 hours prior to receiving the first dose of study medication, for women of 
childbearing potential only. 
 
 
3.18 
Female subjects of childbearing potential must be willing to use an adequate 
method of contraception for the course of the study through 120 days after the 
last dose of the study medication. 
Note: Abstinence is acceptable if this is the usual lifestyle and preferred 
contraception for the subject 

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3.19 
Male subjects of childbearing potential must agree to use an adequate method of 
contraception for the course of the study through 120 days after the last dose of 
the study medication. 
Note: Abstinence is acceptable if this is the usual lifestyle and preferred 
contraception for the subject 
3.20 a 
Provide written informed consent. 
3.20b 
Willing to return to enrolling institution for follow-up (during the Active 
Monitoring Phase of the study). 
3.20c 
Willing to provide tissue samples for correlative research purposes (see Section 
17). 
3.2 
Registration – Exclusion Criteria 
3.21 
Any of the following because this study involves: 
an agent that has known genotoxic, mutagenic and teratogenic effects: 
• Pregnant women 
• Nursing women 
• Men or women of childbearing potential who are unwilling to employ 
adequate contraception 
3.22 
Is currently participating and receiving study therapy or have participated in a 
study of an investigational agent and received study therapy or used an 
investigational device <= 4 weeks prior to registration. 
3.23 
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or 
any other form of immunosuppressive therapy <= 7 days prior to registration. 
3.24 
Has a known history of active TB (Bacillus Tuberculosis). 
3.25 
Hypersensitivity to pembrolizumab or any of its excipients. 
3.26 
Has had a prior anti-cancer monoclonal antibody (mAb) <= 4 weeks prior to 
registration or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse 
events due to agents administered more than 4 weeks earlier. 
3.27 
Has had prior chemotherapy, targeted small molecule therapy, or radiation 
therapy <= 2 weeks prior to registration 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. 
3.28 
Has a known additional malignancy that is progressing or requires active 
treatment. Exceptions: basal cell carcinoma of the skin or squamous cell 
carcinoma of the skin that has undergone potentially curative therapy or in situ 
cervical cancer. 
3.29 
Has known active central nervous system (CNS) metastases and/or 
carcinomatous meningitis. Exceptions:subjects with previously treated brain 
metastases may participate provided they are stable (without evidence of 
progression by imaging <= 4 weeks prior to registration and any neurologic 
symptoms have returned to baseline), have no evidence of new or enlarging brain 

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metastases, and are not using steroids for at least <= 7 days prior to registration. 
This exception does not include carcinomatous meningitis which is excluded 
regardless of clinical stability. 
3.30 
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). Note: Replacement therapy (eg., thyroxine, insulin, 
or physiologic corticosteroid replacement therapy for adrenal or pituitary 
insufficiency, etc.) is not considered a form of systemic treatment. 
3.31 
Has a history of non-infectious pneumonitis that required steroids or has current 
pneumonitis. 
3.32 
Has an active infection requiring systemic therapy. 
3.33 
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. 
3.34 
Has known psychiatric or substance abuse disorders that would interfere with 
cooperation with the requirements of the trial. 
3.35 
Is pregnant or breastfeeding, or expecting to conceive or father children within 
the projected duration of the trial, starting with the screening visit through 120 
days after the last dose of trial treatment. 
3.36 
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 
3.37 
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 
antibodies). 
3.38 
Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV 
RNA [qualitative] is detected). 
3.39 
Has received a live vaccine <= 30 days prior to registration. 
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. 
 
3.39a 
Sezary syndrome patients with high blood burden requiring immediate 
cytoreduction. 

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4.0 
Test Schedule 
4.1 
Test schedule for Mycosis Fungoides 
 
Tests and procedures 
≤ 28 days 
prior to 
registration 
Active Monitoring Phase* 
Follow-up* 
prior to 
treatment 
Day 1, 
Cycles 2-47 
prior to 
treatment 
Day 1, 
Cycles 5 
and beyond7 
End of 
treatment 
(21 days 
after last 
dose) 
Clinical 
Follow- 
up 
(30 days 
after 
EOT) 
Clinical 
Follow- 
up visit 
(90 days 
after 
EOT) 
Main study Informed 
Consent 
X 
Inclusion/Exclusion 
Criteria 
X 
Demographics, medical 
history 
X 
X 
Ht and Wt** 
X 
X 
X 
Vital signs 
Blood pressure 
Pulse 
Temperature 
X 
X 
X 
X 
Prior and Concomitant 
Medication Review 
X 
X 
Post-study Anticancer 
therapy status 
X 
X 
Adverse event assessment 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
X 
X 
X 
Dermatology ExamR 
X 
X 
X 
X 
X 
X 
Standardized Clinical 
PhotographyR 
X 
X 
X 
X 
X 
X 
Skin Biopsy 
X 
XR 
ECOG PS 
X 
X 
X 
mSWAT 
X 
X 
X 
X 
X 
X 
Pregnancy test1 
X 
Hematology group 
CBC with Diff 
X 
X 
X 
X 
X 
Chemistry group2 
X 
X 
X 
X 
X 
Urinalysis 
X 
PT/INR and PTT 
X 
T3, FT4, and TSH3 
X 
X 
X 
X 
X 
Tumor Imaging4 
X 
X 
X 
T and B-cell 
Quantitation5 
X 
XR 
XR 
Mandatory Research 
tissue specimens (see 
Section 17.0) 6,R, 
X 
X 
Cycle = 21 days 
*Window for all visits = ± 3 days 
1. For women of childbearing potential only. Must be done ≤ 72hrs prior to treatment and if clinically 

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indicated. 
2. Chemistry panel: Albumin, total bilirubin, direct bilirubin, calcium, carbon dioxide (bicarbonate), 
chloride, creatinine, glucose, alkaline phosphatase , potassium, total protein, sodium, aspartate amino 
transferase (AST) (SGOT), alanine amino transferase (ALT) (SGPT), urea nitrogen (BUN) 
3. Repeat every other cycle starting on Day 1, Cycle 2. 
4. Whole body CT/PET. 1 Week after the end of Cycle 4 during course of treatment and then, at the End 
of Treatment Visit. 
5. 1 Week after the end of Cycle 4 during course of treatment and then, at the End of Treatment Visit. 
6. Tissue specimens (Skin Biopsy) will be collected and submitted after registration and Cycle 2, Day 
15 only. (See Section 17.0) 
7. Cycle 1 day 1 prior to treatment is recorded as baseline, Prior to treatment Day 1 Cycles 2-4 is 
recorded in the data base as end of cycles 1-3, Prior to treatment Day 1 Cycles 5 and beyond is 
recorded in the database as end of cycle 4 and beyond. 
**Ht not required after registration. 
R  Research funded (see Section 19.0) 

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4.2 
Survival Follow-up 
 
Survival Follow-up 
q. 3 
months 
until PD 
At PD 
After PD 
q. 3 months 
Death 
New Primary 
Survival Follow-up 
X 
X 
X 
X 
At each occurrence 
1. If a patient is still alive 2.5 year after registration, no further follow-up is required. 
 
5.0 
Stratification Factors OR Grouping Factor: 
None. 
 
6.0 
Registration Procedures 
6.1 
Registration: 
6.11 
Registering a patient 
To register a patient, access the Mayo Clinic Cancer Center (MCCC) web page 
and enter the registration/randomization application. The registration/ 
randomization application is available 24 hours a day, 7 days a week. Back up 
and/or system support contact information is available on the website. If unable 
to access the website, call the MCCC Registration Office at 
 
between the hours of 8 a.m. and 4:30 p.m. Central Time (Monday through 
Friday). 
The instructions for the registration/randomization application are available on 
the MCCC web page 
and detail the 
process for completing and confirming patient registration. Prior to initiation of 
protocol treatment, this process must be completed in its entirety and an MCCC 
subject ID number must be available as noted in the instructions. It is the 
responsibility of the individual registering the patient to confirm the process has 
been successfully completed prior to release of the study agent. Patient 
registration via the registration/randomization application can be confirmed in 
any of the following ways: 
• 
Contact the MCCC Registration Office 
 If the patient 
was fully registered, the MCCC Registration Office staff can access the 
information from the centralized database and confirm the registration. 
• 
Refer to “Instructions for Remote Registration” in section 
“Finding/Displaying Information about A Registered Subject.” 
6.2 
Verification of materials 
Prior to accepting the registration, registration/randomization application will verify the 
following: 
• 
IRB approval at the registering institution 
• 
Patient eligibility 
• 
Existence of a signed consent form 
• 
Existence of a signed authorization for use and disclosure of protected health 
information 
6.3 
Documentation of IRB approval 

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Documentation of IRB approval must be on file in the Registration Office before an 
investigator may register any patients. 
In addition to submitting initial IRB approval documents, ongoing IRB approval 
documentation must be on file (no less than annually) at the Registration Office (fax: 
). If the necessary documentation is not submitted in advance of attempting 
patient registration, the registration will not be accepted and the patient may not be 
enrolled in the protocol until the situation is resolved. 
When the study has been permanently closed to patient enrollment, submission of annual 
IRB approvals to the Registration Office is no longer necessary. 
6.4 
Correlative Research 
A mandatory correlative research component is part of this study, the patient will be 
automatically registered onto this component (see Sections 17.1). 
6.5 
Treatment on protocol 
Treatment on this protocol must commence at Mayo Clinic Florida under the supervision 
of a dermatologist and medical oncologist. 
6.6 
Treatment start 
Treatment cannot begin prior to registration and must begin ≤28 days after registration. 
6.7 
Pretreatment 
Pretreatment tests/procedures (see Section 4.0) must be completed within the guidelines 
specified on the test schedule. 
6.8 a 
Baseline symptoms 
All required baseline symptoms (see Section 10.6) must be documented and graded. 
6.8b 
Study drug 
Study drug is available on site. 
6.8c 
Study Conduct 
The clinical trial will be conducted in compliance with regulations (21 CFR 312, 50, and 
56), guidelines for Good Clinical Practice (ICH Guidance E6), and in accordance with 
general ethical principles outlined in the Declaration of Helsinki; informed consent will 
be obtained from all participating patients; the protocol and any amendments will be 
subject to approval by the designated IRB prior to implementation, in accordance with 
21 CFR 56.103(a); and subject records will be stored in a secure location and subject 
confidentiality will be maintained. The investigator will be thoroughly familiar with the 
appropriate use of the study drug as described in the protocol and Investigator’s 
Brochure. Essential clinical documents will be maintained to demonstrate the validity of 
the study and the integrity of the data collected. Master files should be established at the 
beginning of the study, maintained for the duration of the study and retained according to 
the appropriate regulations. 

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7.0 
Protocol Treatment 
7.1 
Treatment Schedule 
 
 
Agent 
Dose 
Route 
Day 
Cycles 
Pembrolizumab 
200 mg 
IV 
Day 1 
q3 weeks 
until 
disease 
progression, 
intolerable 
toxicity, or 
CR for a 
maximum 
duration of 
24 months 
 
 
Protocol treatment should be administered on Day 1 of each cycle after all 
procedures/assessments have been completed as detailed on the Test Schedule (Section 
4.0). Trial treatment may be administered up to 3 days before or after the scheduled Day 
1 of each cycle due to administrative reasons. 
 
All trial treatments will be administered on an outpatient basis. 
 
Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks. 
Sites should make every effort to target infusion timing to be as close to 30 minutes as 
possible. However, given the variability of infusion pumps from site to site, a window of -
5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 
min). 
 
The Pharmacy Manual contains specific instructions for the preparation of the 
pembrolizumab infusion fluid and administration of infusion solution. 
 
8.0 
Dosage Modification Based on Adverse Events 
Strictly follow the modifications in this table for the first two cycles, until individual treatment 
tolerance can be ascertained. Thereafter, these modifications should be regarded as guidelines to 
produce mild-to-moderate, but not debilitating, side effects. If multiple adverse events are seen, 
administer dose based on greatest reduction required for any single adverse event observed. 
Reductions or increases apply to treatment given in the preceding cycle and are based on adverse 
events observed since the prior dose. 
→ ALERT: 
ADR reporting may be required for some adverse events (See Section 10.0) ← 
 
 
  Use the NCI Common Terminology Criteria for Adverse Events (CTCAE) current version 5.0* 
unless otherwise specified   
* 
Located at 
 

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8.1 
Dose Modifications Based on Adverse Events 
 
 
CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Cardiac disorders 
Myocarditis 
pembrolizumab Hold if grade 1 or 2. Administer 
corticosteroids as clinically indicated. 
Discontinue if Grade 3 or 4. 
Pembrolizumab should be 
permanently discontinued if AE does 
not resolve within 12 weeks of last 
dose or corticosteroids cannot be 
reduced to ≤ 10 mg prednisone or 
equivalent per day within 12 weeks 
and continue to survival follow-up. 
Endocrine disorders 
Hyperthyroidism 
pembrolizumab Continue if grade 2. Treat with non- 
selective beta-blockers (e.g. 
propranolol) or thionamides as 
appropriate. 
1Hold or discontinue if grade 3 or 4. 
If discontinue, continue to survival 
follow-up. Pembrolizumab should be 
permanently discontinued if AE does 
not resolve within 12 weeks of last 
dose and continue to survival follow- 
up. 
Hypophysitis 
pembrolizumab Hold if grade 2. Administer 
corticosteroids and initiate hormonal 
replacements as clinically indicated. 
1Hold or discontinue if grade 3 or 4. 
Pembrolizumab should be 
permanently discontinued if AE does 
not resolve within 12 weeks of last 
dose or corticosteroids cannot be 
reduced to ≤ 10 mg prednisone or 
equivalent per day within 12 weeks 
and continue to survival follow-up. 
Hypothyroidism 
pembrolizumab Continue if grade 2-4. Initiate thyroid 
replacement hormones (e.g. 
levothyroxine or liothyroinine) per 
standard of care. Pembrolizumab 
should be permanently discontinued if 
AE does not resolve within 12 weeks 
of last dose and continue to survival 
follow-up. 

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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Gastrointestinal 
disorders 
Diarrhea or Colitis 
pembrolizumab Hold if grade 2-3. 
Discontinue if Grade 4 or if AE does 
not resolve within 12 weeks of last 
dose or inability to reduce 
corticosteroid to 10 mg or less 
prednisone or equivalent per day 
within 12 weeks and continue to 
survival follow-up. 
Immune System 
disorders 
All other immune- 
related AEs 
pembrolizumab Hold if intolerable/persistent grade 2. 
Administer corticosteroids as 
clinically indicated. Hold if grade 3 
AE, unless the event is Gullian-Barre 
Syndrome and/or Encephalitis, then, 
pembrolizumab should be 
discontinued. If AE does not resolve 
within 12 weeks of last dose or 
corticosteroids cannot be reduced to ≤ 
10 mg prednisone or equivalent per 
day within 12 weeks and continue to 
survival follow-up. Pembrolizumab 
should be discontinued if grade 4 AE 
or recurrent grade 3. 
Investigations 
AST / ALT 
elevation or Increased 
Bilirubin 
pembrolizumab Hold if grade 2. Administer 
corticosteroids (initial dose of 1- 
2mg/kg prednisone or equivalent) 
followed by taper. Discontinue if 
Grade 3 or 4 or if AE does not resolve 
within 12 weeks of last dose or 
inability to reduce corticosteroid to 10 
mg or less prednisone or equivalent 
per day within 12 weeks and continue 
to survival follow-up. 
Metabolism and 
nutrition disorders 
Type 1 diabetes mellitus 
(T1DM) or 
Hyperglycemia 
pembrolizumab Hold if Newly onset T1DM or 
Grade 3 or 4 hyperglycemia 
associated with evidence of β-cell 
failure. Initiate insulin replacement 
therapy for subjects with T1DM. 
Administer anti-hyperglycemic in 
subjects with hyperglycemia. 
Discontinue if AE does not resolve 
within 12 weeks of last dose and 
continue to survival follow-up. 

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CTCAE 
System/Organ/Class 
(SOC) 
ADVERSE EVENT 
AGENT 
ACTION** 
Renal and urinary 
disorders 
Nephritis 
pembrolizumab Hold if grade 2. Administer 
corticosteroids (prednisone 1-2mg/kg 
or equivalent) followed by taper. 
Discontinue if grade 3 or 4 or if AE 
does not resolve within 12 weeks of 
last dose or inability to reduce 
corticosteroid to 10 mg or less 
prednisone or equivalent per day 
within 12 weeks and continue to 
survival follow-up. 
Respiratory, thoracic 
and mediastinal 
disorders 
Pneumonitis 
pembrolizumab Hold if grade 2. Administer 
corticosteroids (initial dose of 1- 
2mg/kg prednisone or equivalent) 
followed by taper. Discontinue if 
recurrent grade 2, if grade 3 or 4, or if 
AE does not resolve within 12 weeks 
of last dose or inability to reduce 
corticosteroid to 10 mg or less 
prednisone or equivalent per day 
within 12 weeks and continue to 
survival follow-up. 
Skin and subcutaneous 
tissue disorders 
Stevens-Johnson 
syndrome/ toxic 
epidermal necrolysis 
pembrolizumab Hold if grade 3. Discontinue if grade 
4. Discontinue if AE does not resolve 
within 12 weeks of last dose and 
continue to survival follow-up. 
** Use the following to describe actions in the Action column: 
 Omit = The current dose(s) for the specified drug(s) during a cycle is skipped. The 
patient does not make up the omitted dose(s) at a later time. 
 Hold/Delay = The current dose(s) of all drugs during a cycle is delayed. The patient 
does make up the delayed dose(s) when the patient meets the protocol criteria to restart 
drugs. 
 Discontinue = The specified drug(s) are totally stopped. 
NOTES: 
• 
1Withhold or permanently discontinue pembrolizumab is at the discretion of the investigator or treating 
physician. 
• 
For subjects with Grade 3 or 4 immune-related endocrinopathy where withhold of pembrolizumab is 
required, pembrolizumab may be resumed when AE resolves to ≤ Grade 2 and is controlled with 
hormonal replacement therapy or achieved metabolic control (in case of T1DM) 

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9.0 
Ancillary Treatment/Supportive Care 
9.1 
Full supportive care 
Patients should receive full supportive care while on this study. This includes blood 
product support, antibiotic treatment, and treatment of other newly diagnosed or 
concurrent medical conditions. All blood products and concomitant medications such as 
antidiarrheals, analgesics, and/or antiemetics received from the first day of study 
treatment administration until 30 days after the final dose will be recorded in the medical 
records. 
9.2 
Blood products and growth factors 
Blood products and growth factors should be utilized as clinically warranted and 
following institutional policies and recommendations. The use of growth factors should 
follow published guidelines of the Journal of Clinical Oncology, Volume 33, No 28 
(October 1), 2015: pp. 3199-3212 (WBC growth factors) AND Journal of Clinical 
Oncology, Volume 28, No 33 (November 20), 2010: pp. 4955-5010 
(darbepoetin/epoetin). 
9.3 
Antiemetics 
Antiemetics may be used at the discretion of the attending physician. 
9.4 
Diarrhea 
Diarrhea could be managed conservatively with loperamide. The recommended dose of 
loperamide is 4 mg at first onset, followed by 2 mg every 2-4 hours until diarrhea free 
(maximum 16 mg/day). 
In the event of Grade 3 or 4 diarrhea, the following supportive measures are allowed: 
hydration, octreotide, and antidiarrheals. 
If diarrhea is severe (requiring intravenous rehydration) and/or associated with fever or 
severe neutropenia (Grade 3 or 4), broad-spectrum antibiotics must be prescribed. 
Patients with severe diarrhea or any diarrhea associated with severe nausea or vomiting 
should be hospitalized for intravenous hydration and correction of electrolyte 
imbalances. 
9.5 
Concomitant Medications/Vaccinations (allowed & prohibited) 
Medications or vaccinations specifically prohibited in the exclusion criteria are not 
allowed during the ongoing trial. If there is a clinical indication for one of these or other 
medications or vaccinations specifically prohibited during the trial, discontinuation from 
trial therapy or vaccination may be required. The investigator should discuss any 
questions regarding this with the Merck Clinical team. The final decision on any 
supportive therapy or vaccination rests with the investigator and/or the subject's primary 
physician. 
 
9.51 
Acceptable Concomitant Medications 
All treatments that the investigator considers necessary for a subject’s welfare 
may be administered at the discretion of the investigator in keeping with the 
community standards of medical care. All concomitant medication will be 
recorded in the medical record including all prescription, over-the-counter 
(OTC), herbal supplements, and IV medications and fluids. If changes occur 
during the trial period, documentation of drug dosage, frequency, route, and date 
may also be included in the medical record. All concomitant medications 
received within 28 days before the first dose of trial treatment and 30 days after 
the last dose of trial treatment should be recorded. Concomitant medications 

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administered after 30 days after the last dose of trial treatment should be recorded 
for SAEs and ECIs. 
 
9.52 
Prohibited Concomitant Medications 
Subjects are prohibited from receiving the following therapies during the 
Screening and Treatment Phase (including retreatment of patients who develop 
new skin disease after achieving a complete cutaneous response) of this trial: 
• 
Antineoplastic systemic chemotherapy or biological therapy 
• 
Immunotherapy not specified in this protocol 
• 
Chemotherapy not specified in this protocol 
• 
Investigational agents other than pembrolizumab 
• 
Radiation therapy 
o Note: Radiation therapy to a symptomatic solitary lesion or to 
the brain may be allowed at the investigator’s discretion. 
• 
Live vaccines within 30 days prior to the first dose of trial treatment and 
while participating in the trial. Examples of live vaccines include, but are 
not limited to, the following: measles, mumps, rubella, varicella/zoster, 
yellow fever, rabies, BCG, and typhoid vaccine. 
• 
Systemic glucocorticoids for any purpose other than to modulate 
symptoms from an event of clinical interest of suspected immunologic 
etiology. The use of physiologic doses of corticosteroids may be 
approved after consultation with the sponsor. 
 
Subjects who, in the assessment by the investigator, require the use of any of the 
aforementioned treatments for clinical management should be removed from the 
trial. Subjects may receive other medications that the investigator deems to be 
medically necessary. 
 
The Exclusion Criteria describes other medications which are prohibited in this 
trial. 
 
There are no prohibited therapies during the Post-Treatment Follow-up Phase. 
9.6 a 
Toxicity management for immune-related AEs associated with pembrolizumab 
AEs associated with pembrolizumab exposure may represent an immunologic etiology. 
These immune-related AEs (irAEs) may occur shortly after the first dose or several 
months after the last dose of pembrolizumab treatment and may affect more than one 
body system simultaneously. Therefore, early recognition and initiation of treatment is 
critical to reduce complications. Based on existing clinical trial data, most irAEs were 
reversible and could be managed with interruptions of pembrolizumab, administration of 
corticosteroids and/or other supportive care. For suspected irAEs, ensure adequate 
evaluation to confirm etiology or exclude other causes. Additional procedures or tests 
such as bronchoscopy, endoscopy, skin biopsy may be included as part of the evaluation. 
Based on the severity of irAEs, withhold or permanently discontinue pembrolizumab and 
administer corticosteroids. Dose modification and toxicity management guidelines for 
AEs associated with pembrolizumab are provided in the table in Section 8.1. 
 
 
9.6b 
Toxicity management of infusion-reactions related to pembrolizumab 

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Pembrolizumab may cause severe or life threatening infusion-reactions including severe 
hypersensitivity or anaphylaxis. Signs and symptoms usually develop during or shortly 
after drug infusion and generally resolve completely within 24 hours of completion of 
infusion. Dose modification and toxicity management guidelines on pembrolizumab 
associated infusion reaction are provided in the table below. 
 
NCI CTCAE Grade 
Treatment 
Premedication at 
Subsequent Dosing 
Grade 1 
Mild reaction; infusion 
interruption not 
indicated; intervention 
not indicated 
Increase monitoring of vital signs as medically 
indicated until the subject is deemed medically 
stable in the opinion of the investigator. 
None 
Grade 2 
Requires therapy or 
infusion interruption but 
responds promptly to 
symptomatic treatment 
(e.g., antihistamines, 
NSAIDs, narcotics, IV 
fluids); prophylactic 
medications indicated 
for ≤24 hrs 
Stop Infusion. 
Additional appropriate medical therapy may 
include but is not limited to: 
IV fluids 
Antihistamines 
NSAIDs 
Acetaminophen 
Narcotics 
Increase monitoring of vital signs as medically 
indicated until the subject is deemed medically 
stable in the opinion of the investigator. 
If symptoms resolve within 1 hour of stopping 
drug infusion, the infusion may be restarted at 
50% of the original infusion rate (e.g. from 100 
mL/hr to 50 mL/hr). Otherwise dosing will be 
held until symptoms resolve and the subject 
should be premedicated for the next scheduled 
dose. 
Subjects who develop Grade 2 toxicity despite 
adequate premedication should be permanently 
discontinued from further study drug 
treatment 
Subject may be premedicated 
1.5h (± 30 minutes) prior to 
infusion of pembrolizumab 
with: 
Diphenhydramine 50 mg po 
(or equivalent dose of 
antihistamine). 
Acetaminophen 500-1000 mg 
po (or equivalent dose of 
analgesic). 
Grades 3 or 4 
Grade 3: 
Stop Infusion. 
Additional appropriate medical therapy may 
No subsequent dosing 
Prolonged (i.e., not 
include but is not limited to: 
rapidly responsive to 
Epinephrine** 
symptomatic medication 
IV fluids 
and/or brief interruption 
Antihistamines 
of infusion); recurrence 
NSAIDs 
of symptoms following 
Acetaminophen 
initial improvement; 
Narcotics 
hospitalization indicated 
Oxygen 
for other clinical 
Pressors 
sequelae (e.g., renal 
Corticosteroids 
impairment, pulmonary 
Increase monitoring of vital signs as medically 
infiltrates) 
indicated until the subject is deemed medically 
Grade 4: 
stable in the opinion of the investigator. 
Life-threatening; 
Hospitalization may be indicated. 
pressor or ventilatory 
**In cases of anaphylaxis, epinephrine should be 
support indicated 
used immediately. 
Subject is permanently discontinued from 
further study drug treatment. 

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Other allowed dose interruption for pembrolizumab 
Pembrolizumab may be interrupted for situations other than treatment-related AEs such 
as medical / surgical events or logistical reasons not related to study therapy. Subjects 
should be placed back on study therapy within 3 weeks of the scheduled interruption, 
unless otherwise discussed with the Sponsor. The reason for interruption should be 
documented in the patient's study record. 
9.6c 
Diet 
Subjects should maintain a normal diet unless modifications are required to manage an 
AE such as diarrhea, nausea or vomiting. 
9.6d 
Contraception 
Pembrolizumab may have adverse effects on a fetus in utero. Furthermore, it is not 
known if pembrolizumab has transient adverse effects on the composition of sperm. 
 
For this trial, male subjects will be considered to be of non-reproductive potential if they 
have azoospermia (whether due to having had a vasectomy or due to an underlying 
medical condition). 
 
Female subjects will be considered of non-reproductive potential if they are either: 
(1) postmenopausal (defined as at least 12 months with no menses without an 
alternative medical cause; in women < 45 years of age a high follicle 
stimulating hormone (FSH) level in the postmenopausal range may be used to 
confirm a post-menopausal state in women not using hormonal contraception 
or hormonal replacement therapy. In the absence of 12 months of amenorrhea, 
a single FSH measurement is insufficient.); 
 
OR 
 
(2) have had a hysterectomy and/or bilateral oophorectomy, bilateral 
salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to 
screening; 
 
OR 
 
(3) has a congenital or acquired condition that prevents childbearing. Female 
and male subjects of reproductive potential must agree to avoid becoming 
pregnant or impregnating a partner, respectively, while receiving study drug 
and for 120 days after the last dose of study drug by complying with one of 
the following: 
 
(1) practice abstinence† from heterosexual activity; 
OR 
(2) use (or have their partner use) acceptable contraception during heterosexual activity. 
Appropriate resuscitation equipment should be available at the bedside and a physician readily available during the period of 
drug administration. 
For further information, please refer to the Common Terminology Criteria for Adverse Events v5.0 (CTCAE) at 
 

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Acceptable methods of contraception are‡: 
Single method (one of the following is acceptable): 
o intrauterine device (IUD) 
o vasectomy of a female subject’s male partner 
o contraceptive rod implanted into the skin 
Combination method (requires use of two of the following): 
o diaphragm with spermicide (cannot be used in conjunction with cervical 
cap/spermicide) 
o cervical cap with spermicide (nulliparous women only) 
o contraceptive sponge (nulliparous women only) 
o male condom or female condom (cannot be used together) 
o hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or 
progestin- only pill), contraceptive skin patch, vaginal contraceptive ring, or 
subcutaneous contraceptive injection 
 
†Abstinence (relative to heterosexual activity) can be used as the sole method of 
contraception if it is consistently employed as the subject’s preferred and usual lifestyle 
and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic 
abstinence (e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and 
withdrawal are not acceptable methods of contraception. 
‡If a contraceptive method listed above is restricted by local regulations/guidelines, then 
it does not qualify as an acceptable method of contraception for subjects participating at 
sites in this country/region. 
Subjects should be informed that taking the study medication may involve unknown risks 
to the fetus (unborn baby) if pregnancy were to occur during the study. In order to 
participate in the study subjects of childbearing potential must adhere to the contraception 
requirement (described above) from the day of study medication initiation(or 14 days 
prior to the initiation of study medication for oral contraception) throughout the study 
period up to 120 days after the last dose of trial therapy. If there is any question that a 
subject of childbearing potential will not reliably comply with the requirements for 
contraception, that subject should not be entered into the study. 
9.6e   Use in Pregnancy 
If a patient inadvertently becomes pregnant while on treatment with pembrolizumab, the 
patient will immediately be removed from the study. The site will contact the patient at 
least monthly and document the patient’s status until the pregnancy has been completed 
or terminated. The outcome of the pregnancy will be reported to Mayo Clinic and to 
Merck without delay and within 24 hours to Mayo Clinic and within 2 working days to 
Merck if the outcome is a serious adverse experience (e.g., death, abortion, congenital 
anomaly, or other disabling or life-threatening complication to the mother or newborn). 
 
The study investigator will make every effort to obtain permission to follow the outcome 
of the pregnancy and report the condition of the fetus or newborn. If a male subject 
impregnates his female partner the study personnel at the site must be informed 
immediately and the pregnancy reported to Mayo Clinic and to Merck and followed as 
described above. 

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9.6f 
Use in Nursing Women 
Since many drugs are excreted in human milk, and because of the potential for serious 
adverse reactions in the nursing infant, patients who are breast-feeding are not eligible for 
enrollment. Specific additional information follows for individual agents used in this 
trial. 
9.6f1 
Pembrolizumab 
It is unknown whether pembrolizumab is excreted in human milk. 

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10.0 
Adverse Event (AE) Monitoring and Reporting 
The site principal investigator is responsible for reporting any/all serious adverse events to the 
sponsor as described within the protocol, regardless of attribution to study agent or treatment 
procedure. 
The sponsor/sponsor-investigator is responsible for notifying FDA and all participating 
investigators in a written safety report of any of the following: 
• 
Any suspected adverse reaction that is both serious and unexpected. 
• 
Any findings from laboratory animal or in vitro testing that suggest a significant risk for 
human subjects, including reports of mutagenicity, teratogenicity, or carcinogenicity. 
• 
Any findings from epidemiological studies, pooled analysis of multiple studies, or 
clinical studies, whether or not conducted under an IND and whether or not conducted by 
the sponsor, that suggest a significant risk in humans exposed to the drug 
• 
Any clinically important increase in the rate of a serious suspected adverse reaction over 
the rate stated in the protocol or Investigator’s Brochure (IB). 
Summary of SAE Reporting for this study 
(please read entire section for specific instructions): 
WHO: 
WHAT form: 
WHERE to send: 
Mayo Clinic 
Sites 
Pregnancy Reporting 
 
Mayo Sites – attach to MCCC 
Electronic SAE Reporting Form 
 
 
 
Will automatically be sent to 
 
 
 
 
Mayo Clinic 
Sites 
Mayo Clinic Cancer Center SAE Reporting 
Form
 
 
AND attach 
MedWatch 3500A: 
 
Will automatically be sent to 
 
Mayo Clinic 
Sites 
Merck Global Safety Form 
Merck AE Fax Form 
Submit to Merck Global Safety Attn: 
Worldwide Product Safety; FAX 
 

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Definitions 
Adverse Event 
Any untoward medical occurrence associated with the use of a drug in humans, whether or 
not considered drug related. 
Suspected Adverse Reaction 
Any adverse event for which there is a reasonable possibility that the drug caused the adverse 
event. 
Expedited Reporting 
Events reported to sponsor within 24 hours, 5 days or 10 days of study team becoming aware 
of the event. 
Routine Reporting 
Events reported to sponsor via case report forms 
Events of Interest 
Events that would not typically be considered to meet the criteria for expedited reporting, but 
that for a specific protocol are being reported via expedited means in order to facilitate the 
review of safety data (may be requested by the FDA or the sponsor). 
10.1 
Adverse Event Characteristics 
CTCAE term (AE description) and grade: The descriptions and grading scales found 
in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 
5.0 will be utilized for AE reporting. All appropriate treatment areas should have access 
to a copy of the CTCAE version 5.0. A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP web site: 
 
a. Identify the grade and severity of the event using the CTCAE version 5.0. 
b. Determine whether the event is expected or unexpected (see Section 10.2). 
c. Determine if the adverse event is related to the study intervention (agent, treatment or 
procedure) (see Section 10.3). 
d. Determine whether the event must be reported as an expedited report. If yes, 
determine the timeframe/mechanism (see Section 10.4). 
e. Determine if other reporting is required (see Section 10.5). 
f. Note: All AEs reported via expedited mechanisms must also be reported via the 
routine data reporting mechanisms defined by the protocol (see Sections 10.6 and 
18.0). 
NOTE: A severe AE is NOT the same as a serious AE, which is defined in Section 10.4. 
10.2 
Expected vs. Unexpected Events 
Expected events - are those described within the Section 15.0 of the protocol, the study 
specific consent form, package insert (if applicable), and/or the investigator brochure, (if 
an investigator brochure is not required, otherwise described in the general 
investigational plan). 
Unexpected adverse events or suspected adverse reactions are those not listed in Section 
15.0 of the protocol, the study specific consent form, package insert (if applicable), or in 
the investigator brochure (or are not listed at the specificity or severity that has been 
observed); if an investigator brochure is not required or available, is not consistent with 
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Unexpected also refers to adverse events or suspected adverse reactions that are 
mentioned in the investigator brochure as occurring with a class of drugs but have not 
been observed with the drug under investigation. 
An investigational agent/intervention might exacerbate the expected AEs associated with a 
commercial agent. Therefore, if an expected AE (for the commercial agent) occurs with a 
higher degree of severity or specificity, expedited reporting is required. 
NOTE: *The consent form may contain study specific information at the discretion of the 
Principal Investigator; it is possible that this information may NOT be included in the 
protocol or the investigator brochure. Refer to protocol or IB for reporting needs. 
10.3 
Attribution to agent(s) or procedure 
When assessing whether an adverse event (AE) is related to a medical agent(s) medical or 
procedure, the following attribution categories are utilized: 
Definite - The AE is clearly related to the agent(s)/procedure. 
Probable - The AE is likely related to the agent(s)/procedure. 
Possible - The AE may be related to the agent(s)/procedure. 
Unlikely - The AE is doubtfully related to the agent(s)/procedure. 
Unrelated - The AE is clearly NOT related to the agent(s)/procedure. 
10.31 
EXPECTED Serious Adverse Events: Protocol Specific Exceptions to 
Expedited Reporting 
For this protocol only, the following Adverse Events/Grades are expected to occur 
within this population and do not require Expedited Reporting. These events must still 
be reported via Routine Reporting (see Section 10.6).* 
*Report any clinically important increase in the rate of a serious suspected 
adverse reaction (at your study site) over that which is listed in the protocol or 
investigator brochure as an expedited event. 
*Report an expected event that is greater in severity or specificity than expected 
as an expedited event. 
*Specific protocol exceptions to expedited reporting should be reported 
expeditiously by investigators ONLY if they exceed the expected grade of the 
event. 
 
CTCAE 
System Organ Class 
(SOC) 
Adverse event/ Symptoms 
CTCAE Grade at which the event 
will not be reported via expedited 
mechanisms1 
Blood and lymphatic 
system disorders 
Anemia 
≤Grade 4 
Gastrointestinal disorders 
Vomiting 
≤Grade 3 
Nausea 
≤Grade 3 
Diarrhea 
≤Grade 3 
General disorders and 
administrations site 
conditions 
Fatigue 
≤Grade 3 
Malaise 
≤Grade 3 
Investigations 
Neutrophil count decreased 
≤Grade 4 
White blood cell count 
decreased 
≤Grade 4 
Lymphocyte count decreased 
≤Grade 4 
Platelet count decreased 
≤Grade 4 

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CTCAE 
System Organ Class 
(SOC) 
 
Adverse event/ Symptoms 
CTCAE Grade at which the event 
will not be reported via expedited 
mechanisms1 
Skin and subcutaneous 
tissue disorders 
Rash (acneiform or 
maculopapular) 
≤Grade 4 
1 These exceptions only apply if the adverse event does not result in hospitalization. If the adverse 
event results in hospitalization, then the standard expedited adverse events reporting 
requirements must be followed. 
The following hospitalizations are not considered to be SAEs because there is no “adverse event” 
(i.e., there is no untoward medical occurrence) associated with the hospitalization: 
● Hospitalizations for respite care 
● Planned hospitalizations required by the protocol 
● Hospitalization planned before informed consent (where the condition requiring the hospitalization 
has not changed post study drug administration) 
● Hospitalization for elective procedures unrelated to the current disease and/or treatment on this trial 
● Hospitalization for administration of study drug or insertion of access for administration of study 
drug 
● Hospitalization for routine maintenance of a device (e.g., battery replacement) that was in place 
before study entry 
● Hospitalization, or other serious outcomes for signs and symptoms of progression of the cancer. 
10.4 
Expedited Reporting Requirements for IND Agents 
10.41 Late Phase 2 and Phase 3 Studies: Expedited Reporting Requirements for 
Adverse Events that Occur on Studies under an IND within 30 Days of the 
Last Administration of the Investigational Agent/Intervention1, 2 
 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE: Investigators MUST immediately report to the sponsor ANY Serious Adverse Events, whether or not they 
are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
An adverse event is considered serious if it results in ANY of the following outcomes: 
1) 
Death 
2) 
A life-threatening adverse event 
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours 
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions 
5) 
A congenital anomaly/birth defect. 
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the sponsor within 
the timeframes detailed in the table below. 
Hospitalization 
Grade 1 
Timeframes 
Grade 2 
Timeframes 
Grade 3 Timeframes 
Grade 4 & 5 
Timeframes 
Resulting in 
Hospitalization 
≥24 hrs 
7 Calendar Days 
24-Hour 
3 Calendar 
Days 

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Not resulting in 
Hospitalization 
≥24 hrs 
Not required 
7 Calendar Days 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 3 Calendar Days” - The AE must initially be reported within 24 hours of learning of the AE, 
followed by a complete expedited report within 3 calendar days of the initial 24-hour report. 
o “7 Calendar Days” - A complete expedited report on the AE must be submitted within 7 calendar days 
of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows: 
Expedited 24-hour notification followed by complete report within 3 calendar days for: 
• 
All Grade 4, and Grade 5 AEs 
Expedited 7 calendar day reports for: 
• Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization 
• Grade 3 adverse events 
2 For studies using PET or SPECT IND agents, the AE reporting period is limited to 10 radioactive half-lives, 
rounded UP to the nearest whole day, after the agent/intervention was last administered. Footnote “1” above 
applies after this reporting period. 
Effective Date: May 5, 2011 
NOTE: Refer to Section 10.31 for exceptions to Expedited Reporting 
 
10.42 General reporting instructions 
 
The Mayo IND and/or MCCC Compliance will assist the sponsor-investigator in 
the processing of expedited adverse events and forwarding of suspected 
unexpected serious adverse reactions (SUSARs) to the FDA and IRB. 
Use Mayo Expedited Event Report form 
 
for investigational agents or 
commercial/investigational agents on the same arm. 
 
Submit to Merck Global Safety Attn: Worldwide Product Safety; 
 
 
 
 
Use Sponsor provided forms available in the forms packet and attach to the 
Mayo Expedited Event Report form. 
 
 
10.43 Reporting of re-occurring SAEs 
ALL SERIOUS adverse events that meet the criteria outlined in table10.41 
MUST be immediately reported to the sponsor within the timeframes detailed in 
the corresponding table. This reporting includes, but is not limited to SAEs that 
re-occur again after resolution. 
10.5 
Other Required Reporting 
10.51 Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSOS) 
Unanticipated Problems Involving Risks to Subjects or Others (UPIRTSOS) in 

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general, include any incident, experience, or outcome that meets all of the 
following criteria: 

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1. Unexpected (in terms of nature, severity, or frequency) given (a) the research 
procedures that are described in the protocol-related documents, such as the 

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IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; 
2. Related or possibly related to participation in the research (in this guidance 
document, possibly related means there is a reasonable possibility that the 
incident, experience, or outcome may have been caused by the procedures 
involved in the research); and 
3. Suggests that the research places subjects or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was 
previously known or recognized. 
Some unanticipated problems involve social or economic harm instead of the 
physical or psychological harm associated with adverse events. In other cases, 
unanticipated problems place subjects or others at increased risk of harm, but no 
harm occurs. 
Note: If there is no language in the protocol indicating that pregnancy is not 
considered an adverse experience for this trial, and if the consent form does not 
indicate that subjects should not get pregnant/impregnate others, then any 
pregnancy in a subject/patient or a male patient’s partner (spontaneously 
reported) which occurs during the study or within 120 days of completing the 
study should be reported as a UPIRTSO. 
Mayo Clinic Cancer Center (MCCC) Institutions: 
If the event meets the criteria for IRB submission as a Reportable 
Event/UPIRTSO, provide the appropriate documentation and use the Mayo 
Clinic Cancer Center Expedited Event Report form 
 
The Mayo Clinic Compliance Unit will 
review and process the submission to the Mayo Clinic IRB and work with the 
IND Coordinator for submission to FDA. 

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10.52 Death 
Note: A death on study requires both routine and expedited reporting 
regardless of causality, unless as noted below. Attribution to treatment or 
other cause must be provided. 
Any death occurring within 30 days of the last dose, regardless of attribution to 
an agent/intervention under an IND requires expedited reporting within 24- 
hours. 
Any death occurring greater than 30 days with an attribution of possible, 
probable, or definite to an agent/intervention under an IND requires expedited 
reporting within 24-hours. 
Reportable categories of Death 
• 
Death attributable to a CTCAE term. 
• 
Death Neonatal: A disorder characterized by cessation of life during the 
first 28 days of life. 
• 
Death NOS: A cessation of life that cannot be attributed to a CTCAE term 
associated with Grade 5. 
• 
Sudden death NOS: A sudden (defined as instant or within one hour of the 
onset of symptoms) or an unobserved cessation of life that cannot be 
attributed to a CTCAE term associated with Grade 5. 
• 
Death due to progressive disease that cannot be attributed to a CTCAE term 
associated with Grade 5 should be reported as Grade 5 “Disease 
progression” under the system organ class (SOC) of General disorders and 
administration site conditions. Evidence that the death was a manifestation 
of underlying disease (e.g., radiological changes suggesting tumor growth 
or progression: clinical deterioration associated with a disease process) 
should be submitted. 
10.53 Secondary Malignancy 
• 
A secondary malignancy is a cancer caused by treatment for a previous 
malignancy (e.g., treatment with investigational agent/intervention, radiation 
or chemotherapy). A secondary malignancy is not considered a metastasis of 
the initial neoplasm. 
• 
All secondary malignancies that occur following treatment with an agent under 
an IND will be reported. Three options are available to describe the event: 
o Leukemia secondary to oncology chemotherapy (e.g., Acute Myeloctyic 
Leukemia [AML]) 
o Myelodysplastic syndrome (MDS) 
o Treatment-related secondary malignancy 
• 
Any malignancy possibly related to cancer treatment (including AML/MDS) 
should also be reported via the routine reporting mechanisms outlined in each 
protocol. 
10.54 Second Malignancy 
A second malignancy is one unrelated to the treatment of a prior malignancy (and is 
NOT a metastasis from the initial malignancy). Second malignancies require ONLY 
routine reporting unless otherwise specified. 

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10.55 Pregnancy, Fetal Death, and Death Neonatal 
If a female subject (or female partner of a male subject) taking investigational 
product becomes pregnant, the subject taking should notify the Investigator, and 
the pregnant female should be advised to call her healthcare provider 
immediately. The patient should have appropriate follow-up as deemed necessary 
by her physician. If the baby is born with a birth defect or anomaly, a second 
expedited report is required. 
Prior to obtaining private information about a pregnant woman and her infant, the 
investigator must obtain consent from the pregnant woman and the newborn 
infant’s parent or legal guardian before any data collection can occur. A consent 
form will need to be submitted to the IRB for these subjects if a pregnancy 
occurs. If informed consent is not obtained, no information may be collected. 
In cases of fetal death, miscarriage or abortion, the mother is the patient. In cases 
where the child/fetus experiences a serious adverse event other than fetal death, 
the child/fetus is the patient. 
NOTE: When submitting Mayo Expedited Adverse Event Report reports for 
“Pregnancy”, “Pregnancy loss”, or “Neonatal loss”, the potential risk of exposure 
of the fetus to the investigational agent(s) or chemotherapy agent(s) should be 
documented in the “Description of Event” section. Include any available medical 
documentation. Include this form: 
 
 
10.551 
Pregnancy 
Pregnancy should be reported in an expedited manner as Grade 3 
“Pregnancy, puerperium and perinatal conditions - Other 
(pregnancy)” under the Pregnancy, puerperium and perinatal 
conditions SOC. Pregnancy should be followed until the outcome is 
known. 
10.552 
Fetal Death 
Fetal death is defined in CTCAE as “A disorder characterized by death 
in utero; failure of the product of conception to show evidence of 
respiration, heartbeat, or definite movement of a voluntary muscle after 
expulsion from the uterus, without possibility of resuscitation.” 
Any fetal death should be reported expeditiously, as Grade 4 
“Pregnancy, puerperium and perinatal conditions - Other 
(pregnancy loss)” under the Pregnancy, puerperium and perinatal 
conditions SOC. 
10.553 
Death Neonatal 
Neonatal death, defined in CTCAE as “A disorder characterized by 
cessation of life occurring during the first 28 days of life” that is felt by 
the investigator to be at least possibly due to the investigational 
agent/intervention, should be reported expeditiously. 
A neonatal death should be reported expeditiously as Grade 4 
“General disorders and administration - Other (neonatal loss)” 
under the General disorders and administration SOC. 
10.6 
Required Routine Reporting 

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10.61 Baseline and Adverse Events Evaluations 
Pretreatment symptoms/conditions to be graded at baseline and adverse events to 
be graded at each evaluation. 
Grading is per CTCAE v5.0 unless alternate grading is indicated in the table 
below: 
 
CTCAE SYSTEM 
ORGAN CLASS 
Adverse event/Symptoms 
Baseline 
Each 
evaluation 
Blood and lymphatic 
system disorders 
Febrile neutropenia 
X 
X 
Eye disorders 
Retinal detachment 
X 
X 
Retinal vascular disorder (RVO) 
X 
X 
General disorders and 
administration site 
conditions 
Fatigue 
X 
X 
Gastrointestinal 
Nausea 
X 
X 
disorders 
Vomiting 
X 
X 
# of Stools 
X 
Diarrhea 
X 
Constipation 
X 
X 
Infections and 
infestations 
Sepsis 
X 
X 
Investigations 
CPK (CK) increased 
X 
X 
Creatinine increased 
X 
X 
Neutrophil count decreased 
X 
X 
Platelet count decreased 
X 
X 
Nervous system 
Peripheral sensory neuropathy 
X 
X 
disorders 
Peripheral motor neuropathy 
X 
X 
Skin and 
subcutaneous tissue 
disorders 
Rash, acneiform 
X 
X 
Rash, maculo-papular 
X 
X 
Vascular disorders 
Hypertension 
X 
X 
 
10.62 All other AEs 
Submit via appropriate MCCC Case Report Forms (i.e., paper or electronic, as 
applicable) the following AEs experienced by a patient and not specified in 
Section 10.6: 
10.621 Grade 2 AEs deemed possibly, probably, or definitely related to the study 
treatment or procedure. 
10.622 Grade 3 and 4 AEs regardless of attribution to the study treatment or 
procedure. 
10.623 Grade 5 AEs (Deaths) 

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10.6231 
Any death within 30 days of the patient’s last study 
treatment or procedure regardless of attribution to the study 
treatment or procedure. 
10.6232 
Any death more than 30 days after the patient’s last study 
treatment or procedure that is felt to be at least possibly 
treatment related must also be submitted as a Grade 5 AE, 
with a CTCAE type and attribution assigned. 
10.7 
Late Occurring Adverse Events 
Refer to the instructions in the Forms Packet (or electronic data entry screens, as 
applicable) regarding the submission of late occurring AEs following completion of the 
Active Monitoring Phase (i.e., compliance with Test Schedule in Section 4.0). 
10.8 
Additional Event Reporting Instruction (Merck) 
10.81 All AEs, SAEs and other reportable safety events that occur after the consent 
form is signed but before treatment allocation must be reported by the 
investigator if the participant is receiving placebo run-in or other run-in 
treatment, if the event cause the participant to be excluded from the study, or is 
the result of a protocol-specified intervention, including but not limited to 
washout or discontinuation of usual therapy, diet, or a procedure. 
o All AEs from the time of treatment allocation/randomization 
through 30 days following cessation of study treatment must 
be reported by the investigator. 
o All AEs meeting serious criteria, from the time of treatment 
allocation/randomization through 90 days following 
cessation of study treatment, or 30 days following cessation 
of study treatment if the participant initiates new anticancer 
therapy, whichever is earlier must be reported by the 
investigator. 
o All pregnancies and exposure during breastfeeding, from the 
time of treatment allocation/randomization through 120 days 
following cessation of study treatment, or 30 days following 
cessation of study treatment if the participant initiates new 
anticancer therapy must be reported by the investigator. 
o Additionally, any SAE brought to the attention of an 
investigator at any time outside of the time period specified 
above must be reported immediately by the investigator if 
the event is considered to be drug-related. 
 
Investigators are not obligated to actively seek AE or SAE or other reportable 
safety events in former study participants. However, if the investigator learns of 
any SAE, including a death, at any time after a participant has been discharged 
from the study, and he/she considers the event to be reasonably related to the 
study treatment or study participation, the investigator must promptly notify 
Merck. 
 
10.82 Definition of an Overdose for This Protocol and Reporting of Overdose to the 
Sponsor and to Merck 

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For purposes of this study, an overdose of pembrolizumab will be defined as any 
dose of 1,000 mg or greater (≥5 times the indicated dose). No specific 
information is available on the treatment of overdose of pembrolizumab. In the 
event of overdose, the participant should be observed closely for signs of 
toxicity. Appropriate supportive treatment should be provided if clinically 
indicated. 
 
If an adverse event(s) is associated with (“results from”) the overdose of a Merck 
product, the adverse event(s) is reported as a serious adverse event, even if no 
other seriousness criteria are met. 
 
If a dose of Merck’s product meeting the protocol definition of overdose is taken 
without any associated clinical symptoms or abnormal laboratory results, the 
overdose is reported as a non-serious Event of Clinical Interest (ECI), using the 
terminology “accidental or intentional overdose without adverse effect.” 
 
All reports of overdose with and without an adverse event must be reported 
within 24 hours to the Sponsor and within 2 working days to Merck Global 
Safety. 
 
 
10.83 Reporting of Pregnancy and Lactation to Merck 
Although pregnancy and infant exposure during breast feeding are not considered 
adverse events, it is the responsibility of investigators or their designees to report 
any pregnancy or lactation in a participant (spontaneously reported to them) that 
occurs during the study. 
 
Pregnancies and infant exposures during breastfeeding that occur after the 
consent form is signed but before treatment allocation/randomization must be 
reported by the investigator if they cause the participant to be excluded from the 
trial, or are the result of a protocol-specified intervention, including but not 
limited to washout or discontinuation of usual therapy, diet, placebo treatment or 
a procedure. 
 
Pregnancies and infant exposures during breastfeeding that occur from the time 
of treatment allocation/randomization through 120 days following cessation of 
Sponsor’s product, or 30 days following cessation of treatment if the participant 
initiates new anticancer therapy, whichever is earlier, must be reported by the 
investigator. All reported pregnancies must be followed to the 
completion/termination of the pregnancy. Pregnancy outcomes of spontaneous 
abortion, missed abortion, benign hydatidiform mole, blighted ovum, fetal death, 
intrauterine death, miscarriage and stillbirth must be reported as serious events 
(Important Medical Events). If the pregnancy continues to term, the outcome 
(health of infant) must also be reported. 
 
Such events must be reported within 24 hours to the Sponsor and within 2 
working days to Merck Global Safety. 
 
 
 
10.84 Immediate Reporting of Adverse Events to the Sponsor and to Merck 
A serious adverse event is any adverse event occurring at any dose or during any 
use of Merck’s product that: 

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• 
Results in death; 
• 
Is life threatening; 
• 
Results in persisten or significant disability/incapacity; 
• 
Results in or prolongs an existing inpatient hospitalization; 
• 
Is a congenital anomaly/birth defect; 
• 
Is an other important medical event 
• 
Note: In addition to the above criteria, adverse events meeting either 
of the below criteria, although not serious per ICH definition, are 
reportable to the Merck in the same timeframe as SAEs to meet 
certain local requirements. Therefore, these events are considered 
serious by Merck for collection purposes. 
o Is a new cancer (that is not a condition of the study); 
o Is associated with an overdose. 
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any serious adverse event, or follow up to a serious 
adverse event, including death due to any cause that occurs to any participant 
must be reported within 24 hours to the Sponsor and within 2 working days to 
Merck Global Safety if it causes the participant to be excluded from the trial, or 
is the result of a protocol-specified intervention, including but not limited to 
washout or discontinuation of usual therapy, diet, placebo treatment or a 
procedure. 
 
For the time period beginning at treatment allocation/randomization through 90 
days following cessation of treatment, or 30 days following cessation of 
treatment if the participant initiates new anticancer therapy, whichever is earlier, 
any serious adverse event, or follow up to a serious adverse event, including 
death due to any cause whether or not related to the Merck product, must be 
reported within 24 hours to the Sponsor and within 2 working days to Merck 
Global Safety. 
 
Additionally, any serious adverse event, considered by an investigator who is a 
qualified physician to be related to Merck product that is brought to the attention 
of the investigator at any time following consent through the end of the specified 
safety follow-up period specified in the paragraph above, or at any time outside 
of the time period specified in the previous paragraph also must be reported 
immediately to Merck Global Safety. 
 
All participants with serious adverse events must be followed up for outcome. 
 
SAE reports and any other relevant safety information are to be forwarded 
to the Merck Global Safety facsimile number: 
 
 
A copy of all 15 Day Reports and Annual Progress Reports is submitted as 
required by FDA, European Union (EU), Pharmaceutical and Medical Devices 
agency (PMDA) or other local regulators. Investigators will cross reference this 
submission according to local regulations to the Merck Investigational 
Compound Number (IND, CSA, etc.) at the time of submission. Additionally 
investigators will submit a copy of these reports to Merck & Co., Inc. 
 

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at the time of submission to 
FDA. 
 
10.85 Events of Clinical Interest 
Selected non-serious and serious adverse events are also known as Events of 
Clinical Interest (ECI) and must be reported within 2 working days to Merck 
Global Safety. 
 
 
For the time period beginning when the consent form is signed until treatment 
allocation/randomization, any ECI, or follow up to an ECI, that occurs to any 
participant must be reported within 2 working days to Merck Global Safety if it 
causes the participant to be excluded from the trial, or is the result of a protocol- 
specified intervention, including but not limited to washout or discontinuation of 
usual therapy, diet, placebo treatment or a procedure. 
 
For the time period beginning at treatment allocation/randomization through 90 
days following cessation of treatment, or 30 days following cessation of 
treatment if the participant initiates new anticancer therapy, whichever is earlier, 
any ECI, or follow up to an ECI, whether or not related to Merck product, must 
be reported within 2 working days to Merck Global Safety. 
 
Events of clinical interest for this trial include: 
1. An overdose of Merck product, as defined in Section10.82, that is not 
associated with clinical symptoms or abnormal laboratory results. 
2. An elevated AST or ALT lab value that is greater than or equal to 3X the 
upper limit of normal and an elevated total bilirubin lab value that is 
greater than or equal to 2X the upper limit of normal and, at the same 
time, an alkaline phosphatase lab value that is less than 2X the upper 
limit of normal, as determined by way of protocol-specified laboratory 
testing or unscheduled laboratory testing.* 
 
*Note: These criteria are based upon available regulatory guidance 
documents. The purpose of the criteria is to specify a threshold of 
abnormal hepatic tests that may require an additional evaluation for an 
underlying etiology. 

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11.0 
Treatment Evaluation/Measurement of Effect 
Patients must have measurable disease. 
 
The primary endpoint is the evaluation of cutaneous disease as measured by mSWAT (5). 
Disease progression will also be measured by lymph nodes, visceral disease and blood. 
11.1 
Definitions of Measurable 
11.11 
Measurable Disease 
11.111 A primary cutaneous lesion is measurable if detectable through standard 
full body skin examination. Documentation by color photography is 
required. 
11.112 A visceral lesion is considered measurable if its longest diameter can be 
accurately measured as 2.0 cm with chest x-ray, or as ≥1.0 cm with CT 
scan, CT component of a PET/CT, or MRI. 
11.113 A malignant lymph node is considered measurable if its short axis is 
≥1.5 cm when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). 
11.2 
Evaluation of Measurable Disease 
11.21 Evaluation of primary cutaneous lesion 
 
mSWAT is calculated using body surface area (BSA) of each MF lesion (palm 
plus fingers of the patient ≈ 1% BSA) in each of 12 areas of the body, 
multiplying the sum of the BSA of each lesion type by a weighting factor 
(patch=1, plaque=2, and tumor =4) and generating a sum of the subtotals of each 
lesion subtype. 
 
11.211 Measurement of effect 
• 
Overall cutaneous response rate (ORR) = proportion of patients with 
a 50% or greater reduction of baseline mSWAT score 
• 
Complete cutaneous response rate (CR) = proportion of patients with 
a 100% reduction of baseline mSWAT score 
• 
Cutaneous 90 response rate (CR90) = proportion of patients with a 
90% or greater reduction of baseline mSWAT score without the 
development of new tumors 
• 
Cutaneous partial response rate (PR) = proportion of patients with a 
50-90% baseline reduction of mSWAT score without the 
development of new tumors 
• 
Progressive cutaneous disease (PD) = greater than 25% increase in 
baseline mSWAT or the development of new tumors. However, if in 
the judgement of the investigator, the increase in mSWAT is the 
result of inflammation due to treatment and/or the unmasking of 
subclinical skin involvement, this increase in mSWAT shall not be 
considered evidence of progressive cutaneous disease and the patient 
shall otherwise be classified as stable cutaneous disease (SD). 
• 
Stable cutaneous disease (SD) = <25% increase to <50% reduction 
in baseline mSWAT without the development of new tumors ; or 
patients with a greater than 25% increase baseline mSWAT due to 

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the result of inflammation due to treatment and/or the unmasking of 
subclinical skin involvement. 
• 
Relapsed cutaneous disease = Any disease recurrence in those with 
complete response 
 
11.22 Evaluation of target visceral lesions or target lymph nodes 
 
11.223 Identification of target lesions 
• 
Measurable lesions (as defined in Section 11.1) up to a maximum of 
5 representative of all involved organs, should be identified as 
“Target Lesions” and recorded and measured at baseline. 
• 
Target visceral lesions and target lymph nodes should be selected on 
the basis of their size, be representative of all involved sites of 
disease, but in addition should be those that lend themselves to 
reproducible repeated measurements. It may be the case that, on 
occasion, the largest lesion (or malignant lymph node) does not lend 
itself to reproducible measurements in which circumstance the next 
largest lesion (or malignant lymph node) which can be measured 
reproducibly should be selected. 
11.224 Measurement Methods 
• 
All measurements should be recorded in metric notation (i.e., 
decimal fractions of centimeters) using a ruler or calipers. 
• 
The same method of assessment and the same technique must be 
used to characterize each identified and reported lesion at baseline, at 
the end of cycle 4 and at the end of treatment. 
11.225 Acceptable modality 
• 
Tumor imaging will be performed using a full body PET-CT. If the 
site can document that the CT performed as part of a PET-CT is of 
identical diagnostic quality to a diagnostic CT (with IV and oral 
contrast), then the CT portion of the PET-CT can be used for 
RECIST measurements. 
11.226 Evaluation of target lesions 
• 
Baseline Sum of Dimensions (BSD): A sum of the longest diameter 
for all target visceral lesions plus the sum of the short axis of all the 
target lymph nodes will be calculated and reported as the baseline 
sum of dimensions (BSD). The BSD will be used as reference to 
further characterize any objective tumor response in the measurable 
dimension of the disease. 
• 
Post-Baseline Sum of the Dimensions (PBSD): A sum of the longest 
diameter for all target visceral lesions plus the sum of the short axis 
of all the target lymph nodes will be calculated and reported as the 
post-baseline sum of dimensions (PBSD). If the radiologist is able to 
provide an actual measure for the target visceral lesion (or target 
lymph node), that should be recorded, even if it is below 0.5 cm. If 
the target visceral lesion (or target lymph node) is believed to be 
present and is faintly seen but too small to measure, a default value 
of 0.5 cm should be assigned. If it is the opinion of the radiologist 
that the target visceral lesion or target lymph node has likely 
disappeared, the measurement should be recorded as 0 cm. 

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• 
The minimum sum of the dimensions (MSD) is the minimum of the 
BSD and the PBSD. 
11.227 Measurement of effect 
• 
Complete Response (CR):All of the following must be true: 
a. Disappearance of all visceral lesions. 
b. Each target lymph node must have reduction in short axis to 
<1.0 cm. 
• 
Partial Response (PR): At least a 30% decrease in PBSD (sum of the 
longest diameter for all target visceral lesions plus the sum of the 
short axis of all the target lymph nodes at current evaluation) taking 
as reference the BSD (see Section 11.226). 
 
• 
Progression (PD): At least one of the following must be true: 
a. At least one new malignant lesion, which also includes any 
lymph node that was normal at baseline (<1.0 cm short axis) 
and increased to ≥1.0 cm short axis during follow-up. 
b. At least a 20% increase in PBSD (sum of the longest 
diameter for all target visceral lesions plus the sum of the 
short axis of all the target lymph nodes at current evaluation) 
taking as reference the MSD (Section 11.41). In addition, the 
PBSD must also demonstrate an absolute increase of at least 
0.5 cm from the MSD. 
• 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR, 
nor sufficient increase to qualify for PD taking as reference the 
MSD. 
 
11.3 
Evaluation of peripheral blood 
T and B-cell Quantitation will be utilized to evaluate peripheral blood. CD4 and CD8 
test results will be collected and the ratio CD4:CD8 will be compiled. 
11.31 
Measurement effect 
• 
Complete Response (CR): No blood involvement. 
• 
Partial Response (PR): 50% decrease in CD4 count or CD4:CD8 ratio ≤10. 
• 
Progressive Disease (PD): 50% increase from baseline (≥5,000 CD4+cells in 
blood or CD4:CD8 ratio ≥15). 
• 
Stable Disease (SD): Not CR, PR or PD. 
 
 
11.4 
Measurement at Follow-up Evaluations 
11.41 Cutaneous lesions 
• 
mSWAT will be collected at baseline, end of every cycle of treatment and 
during clinical follow-up at 30 and 90 days. 
• 
mSWAT response will be recorded as per Section 11.211. 
 
11.42 Target visceral lesions and lymph nodes. 

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• 
Subsequent PET-CT scans must be obtained after cycle 4 and the end of 
treatment visit following initial documentation of objective cutaneous 
response status of either complete response (CR) or partial response (PR). 
• 
In the case of stable disease (SD), follow-up measurements must have met 
the SD criteria at least once after study entry at a minimum interval of 3 
weeks. 
• 
The cytological confirmation of the neoplastic origin of any effusion that 
appears or worsens during treatment when the measurable tumor has met 
criteria for response or stable disease is mandatory to differentiate between 
response or stable disease (an effusion may be a side effect of the treatment) 
and progressive disease. 
11.43 Peripheral blood 
T and B-Cell Quantitation will be performed at baseline, end of cycle 4, and at 
end of treatment. 
11.5 
Overall Objective Status 
Overall systemic response rate is defined as 50% or greater reduction of baseline 
mSWAT score without evidence of progressive nodal, visceral, or blood 
involvement. 
 
12.0 
Descriptive Factors 
12.1 
None. 
 
13.0 
Treatment/Follow–up Decision at Evaluation of Patient 
 
 
Reason Off Treatment (from the Off Treatment Form) 
Go to CFU, SFU, or end 
folder rollout 
1 = Treatment (Intervention) Completed Per Protocol Criteria 
CFU 
2 = Patient Withdrawal/Refusal After Beginning Protocol Therapy 
(Intervention) 
SFU 
3 = Adverse Events/Side Effects/Complications 
SFU 
4 = Disease Progression, Relapse During Active Treatment (Intervention) 
SFU 
5 = Alternative Therapy 
No follow-up 
6 = Patient Off-Treatment (Intervention) For Other Complicating Disease 
SFU 
7 = Death On Study 
No follow-up 
8 = Other 
SFU 
10 = Disease Progression Before Active Treatment (Intervention) 
No follow-up 
24 = Patient Withdrawal/Refusal Prior To Beginning Protocol Therapy 
(Intervention) 
No follow-up 
13.1 
Continuation of treatment 
Patients who are CR90, PR, or SD will continue treatment per protocol up to a 
maximum duration of 24 months. . 
13.2 
Progressive disease (PD) 

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Patients who develop PD (non-responders) during cycle 1 will exit the study (no 
follow-up). Patients who develop PD subsequent while receiving therapy will complete 
the End of Treatment visit at the time of PD and repeat staging per protocol, then 
proceed to survival follow-up (Section 4.2). 
13.3 
Off protocol treatment 
Patients who do not develop PD during cycle 1 and go off protocol treatment for reasons 
other than PD within any cycle will proceed to survival follow-up. Note: This does not 
apply to patients receiving alternative therapy. Patients who go off treatment for 
alternative therapy will exit the study (no follow-up). 
Patients who achieve CR at any time will proceed to survival follow-up. 
13.4 
Clinical Follow-up 
Patients achieving CR90, PR, or SD, and who have completed 24 months of treatment 
will be observed for clinical follow-up at 30 and 90 days after the end of treatment, and 
then proceed to survival follow-up. 
13.5 
Duration of therapy for CR 
The maximum duration of therapy is 24 months. Patients who achieve CR during this 
period will be removed from active treatment and will proceed to survival follow-up, 
thus duration of therapy for CR will be 24 months or less. 
13.6 
Duration of therapy for CR90, PR or SD 
Patients who achieve CR90, PR, or SD will continue on therapy up to a maximum 
duration of 24 months.. After 24 months,, the patients will continue to clinical follow-up 
at 30 and 90 days after the last treatment and then proceed to survival follow-up (see 
13.4 above). Subsequent treatment is at the discretion of their attending. 
 
13.7 
Ineligible 
A patient is deemed ineligible if after registration, it is determined that at the time of 
registration, the patient did not satisfy each and every eligibility criteria for study entry. If 
the patient received treatment, the patient may continue treatment at the discretion of the 
physician as long as there are not safety concerns. The patient will continue in the Active 
Monitoring/Treatment phase of the study, as per section 4.0 of the protocol. 
• 
If the patient never received treatment, on-study material must be submitted. Survival 
Follow-up will be required per Section 4.0 of the protocol. 
13.8 
Major violation 
A patient is deemed a major violation, if protocol requirements regarding treatment in 
cycle 1 of the initial therapy are severely violated that evaluability for primary end point 
is questionable. If the patient received treatment, the patient may continue treatment at 
the discretion of the physician as long as there are no safety concerns. The patient will 
continue in the Active Monitoring/Treatment phase of the study, as per section 4.0 of the 
protocol. 
13.9 
Cancel 

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A patient is deemed a cancel if he/she is removed from the study for any reason before 
any study treatment is given. On-study material and the End of Active Treatment/Cancel 
Notification Form must be submitted. No further data submission is necessary. 

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14.0 
Body Fluid Biospecimens 
None. 
15.0 
Drug Information 
IND number (139381) 
• 
Investigator brochure 
Industry-supplied: 
(drug company contact: :
 
15.1 
Pembrolizumab (MK-3475, SCH 900475, Keytruda®) 
15.11 Background: Pembrolizumab is a potent humanized IgG4 monoclonal antibody 
with high specificity of binding to the PD-1 receptor, thus inhibiting its 
interaction with PD-L1 and PD-L2. Based on preclinical in vitro data, 
pembrolizumab has high affinity and potent receptor blocking activity for PD-1. 
 
15.12 Formulation: 
 
Pembrolizumab is available as a liquid 25 mg/mL, 100 mg/vial. 
 
15.13 Preparation and storage: 
 
Vials should be stored in the refrigerator at temperatures between 2-8°C. 
 
Drug concentrate is further diluted with normal saline (or 5% dextrose) in 
the concentration range of 1 to 10 mg/mL. The infusion solution in the IV 
bag should be immediately administered. Diluted pembrolizumab 
solutions may be stored at room temperature for a cumulative period of up 
to 46 hours. This includes room temperature storage of admixture 
solutions in the IV bags and the duration of infusion. The product can also 
be stored under refrigeration at 2°C to 8°C for no more than 96 hours from 
the time of dilution. If refrigerated, the diluted solution must be allowed to 
come to room temperature prior to administration. The solution must be 
discarded after 6 hours at room temperature or 96 hours under 
refrigeration.  
15.14 Administration: Pembrolizumab is administered by intravenous infusion over 
30 minutes via a 0.22 micron in-line filter. The final infusion volume must be 
between 1 and 10 mg/mL. Maximum rate of infusion should not exceed 6.7 
mL/minute through a peripheral or indwelling catheter. Flush the line with 0.9% 
NaCL following the completion of the infusion. 
 
 
15.15 Pharmacokinetic information: 
a) Absorption –Because pembrolizumab is administered intravenously, it 
is immediately and completely bioavailable. Steady-state concentrations 
of pembrolizumab are reached by 16 weeks of repeated dosing with a 
Q3W regimen and the systemic accumulation is 2.1-fold. The peak 
concentration, trough concentration, and area under the plasma 
concentration versus time curve at steady state of pembrolizumab 
increased dose proportionally in the dose range of 2 to 10 mg/kg Q3W. 
b) Distribution – Pembrolizumab has a limited volume of distribution. 

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c) Excretion – CL is approximately 23% lower after achieving maximal 
change at steady state compared with the first dose. The terminal 
elimination half-life (t½) is estimated to be 22 days at steady state. 
d) Metabolism - Pembrolizumab is catabolized through non-specific pathways; 
metabolism does not contribute to its CL. 
 
There are limited clinical studies on the subcutaneous formulation. Model-
based analysis showed an estimated bioavailability of 64% (95% CI: 54% to 
74%; variability, 128% CV). This is consistent with the reported 
bioavailability for other mAbs (range: 50% to 85%) given SC. Clearance was 
the same for the IV and SC formulations. The mean time to achieve maximum 
concentration (Tmax) with pembrolizumab SC was estimated to be 5.5 days 
(range: 3 days to 14 days). 
 
15.16 Potential Drug Interactions: There are no known significant drug 
interactions. 
 
15.17 Known potential adverse events: 
Very common known potential toxicities, ≥ 10%: 
Gastrointestinal disorders: diarrhea, nausea 
Cardiovascular: cardiac arrythmia, peripheral edema 
Dermatologic: pruritis, skin rash, vitiligo 
Endocrine and metabolic: decreased serum bicarbonate, hypercalcemia, 
hypercholesterolemia, hyperglycemia, hyperkalemia, hypertriglyceridemia, 
hypoalbuminemia, hypocalcemia, hypoglycemia, hypokalemia, 
hypomagnesemia, hyponatremia, hypophosphatemia, hypothyroidism, weight 
loss, constipation, decreased appetite, vomiting 
Genitourinary: hematuria, urinary tract infection 
Hematologic and oncologic: anemia, hemorrhage, increased INR, leukopenia, 
lymphocytopenia, neutropenia, prolonged partial thromboplastin time, 
thrombocytopenia Hepatic: hyperbilirubinemia, increased serum alanine 
aminotransferase, increased serum alkaline phosphatase, increased serum 
aspartate aminotransferase 
Infection: infection 
Nervous system: fatigue, headache, pain, peripheral neuropathy 
Neuromuscular & skeletal: arthralgia, asthenia, back pain, musculoskeletal 
pain, myalgia 
Renal: increased serum creatinine 
Respiratory: cough, dyspnea, flu-like symptoms, pneumonia, pneumonitis, 
upper respiratory tract infection 
Miscellaneous: fever 
 
 
 
Common known potential adverse events, ≥1% to < 
10 
Cardiovascular: acute myocardial infarction, cardiac tamponade, facial edema, 
ischemic heart disease, myocarditis, pericardial effusion, pericarditis, 
pulmonary embolism 
Endocrine & metabolic: hyperthyroidism, thyroiditis 
Gastrointestinal: colitis, dysphagia, stomatitis 
Hematologic & oncologic: febrile neutropenia, tumor flare 

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Hepatic: ascites, hepatitis 
Immunologic: antibody development 
Infection: herpes virus infection, herpes zoster infection, sepsis 
Nervous system: altered mental status, confusion, dizziness, insomnia 
Neuromuscular & skeletal: arthritis, myositis, neck pain 
Ophthalmic: uveitis 
Renal: acute kidney injury 
Respiratory: nasopharyngitis, oropharyngeal pain, pleural effusion, respiratory 

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failure 
Miscellaneous: fistula, infusion related reaction 
 
 
Uncommon known potential adverse events , ≥0.1% to <1%: 
Cardiovascular: Vasculitis 
Endocrine & metabolic: adrenocortical insufficiency, diabetic ketoacidosis, 
hypoparathyroidism, hypophysitis, type 1 diabetes mellitus 
Gastrointestinal: duodenitis, gastritis, increased serum amylase, increased 
serum lipase, pancreatitis 
Hematologic & oncologic: aplastic anemia, hemolytic anemia, immune 
thrombocytopenia, immunological signs and symptoms (hemophagocytic 
lymphohistiocytosis), lymphadenitis (histiocytic necrotizing lymphadenitis 
[Kikuchi lymphadenitis]), sarcoidosis 
Hypersensitivity: anaphylaxis 
Immunologic: organ transplant rejection (solid) 
Infection: Systemic inflammatory response syndrome 
Nervous system: demyelinating disease, encephalitis, exacerbation of 
myasthenia gravis, Guillain-Barre syndrome, meningitis, myasthenia 
(myasthenic syndrome), myasthenia gravis, neuropathy (autoimmune), paresis 
(nerve) 
Neuromuscular & skeletal: myelitis, polymyalgia rheumatica, polymyositis, 
rhabdomyolysis 
Ophthalmic: iritis 
Renal: nephritis 

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The risk profile for pembrolizumab also includes two important potential risks: a) 
myasthenic syndrome, and b) an increased risk of severe complications (such as 
early severe graft versus host disease and veno-occlusive disease) of allogeneic 
transplant in patients with hematologic malignancies who have previously been 
treated with PD-1 inhibitors. 
 
Since the last IB, Edition 21, a new identified risk of hypoparathyroidism has 
been added to the warnings and precautions section of the CCDS based on 
routine pharmacovigilance. 
 
Per IB, Edition 23 a new risk of optic neuritis has been added to the 
Postmarketing Experience Adverse Reactions section of the CCDS based on 
routine pharmacovigilance. 
 
Patients with multiple myeloma who were treated with pembrolizumab in 
combination with either pomalidomide or lenalidomide and dexamethasone, had 
an increased number of serious side effects and deaths as compared to patients 
who received only dexamethasone and either pomalidomide or lenalidomide. The 
benefit-risk profile is unfavorable for the combination of pembrolizumab, 
pomalidomide, and dexamethasone in relapsed refractory multiple myeloma, and 
the combination of pembrolizumab, lenalidomide, and dexamethasone in newly 
diagnosed treatment-naive multiple myeloma. 
 
Post marketing reports have identified additional adverse reactions, including arthritis, 
Vogt-Koyanagi-Harada syndrome and hemophagocytic lymphohistiocytosis. Because 
these reactions are reported voluntarily from a population of uncertain size, it is not 
always possible to reliably estimate their frequency or establish a causal relationship 
to drug exposure. 
 
 
15.18 Drug procurement: 
Pembrolizumab will be provided free of charge to study participants by Merck. 
 
15.19 Nursing guidelines 
15.191 Pembrolizumab side effects vary greatly from those of traditional 
chemotherapy and can vary in severity from mild to life threatening. Instruct 
patients to report any side effects to the study team immediately. Side effects 
may be immediate or delayed up to months after discontinuation of therapy. Most 
side effects are reversible with prompt intervention of corticosteroids. 
15.192 Diarrhea can be seen however is less common than that seen with anti- 
CTLA-4 agents. However it can be severe, leading to colonic perforation. 
Instruct patients to report ANY increase in the number of stools and/or change in 
baseline, blood in the stool, abdominal pain to the study team immediately. 
15.193 Rash/pruritus/dermatitis is seen. Patients should report any rash to 
the study team. Treat per section 9.0 and monitor for effectiveness. 

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15.194 Monitor LFT’s closely as elevations in these levels could indicate early 
onset autoimmune hepatitis. Patients should also be instructed to report any 
jaundice, or right upper quadrant pain to the study team immediately. 
15.195 Pneumonitis can be seen and may be mild (only seen on imaging) to 
severe. Patients should be instructed to report any SOB, dyspnea, cough, chest 
pain, etc. to the study team immediately. Patients reporting these symptoms 
should have a pulse ox checked and consider immediate imaging per the treating 
MD. 
15.196 Endocrinopathies (including hypopituitarism, hypothyroidism, 
hypophysistis, and adrenal insufficiency) are seen with this agent. Patients may 
present only with the vague sense of fatigue and “not feeling well” . Additional 
symptoms may be that of nausea, sweating and decreased activity tolerance. 
Instruct patients to report these signs or symptoms immediately and obtain 
appropriate labs as ordered by MD. 
15.197 Patients who are started on steroid therapy for any side effects of 
pembrolizimab toxicity should be instructed to take the steroids as ordered, and 
not to discontinue abruptly as symptoms may return and be severe. Patients may 
be on steroid therapy for weeks. Instruct patients to report any increase or change 
in side effects with any dosage decrease as patients may need a slower taper. 
15.198 Fatigue is common and may or may not be associated with immune 
related side effects. Assess patient’s fatigue level prior to each cycle of therapy 
and report any changes to the study team. 
15.199 a Patients should avoid receiving live vaccines within 30 days of study 
drug administration or per other study guidelines. 
15.199b Patients who have undergone an allogenic bone marrow transplant, have 
an increased risk of severe complications including early GVHD, and 
venoocclusive disease, if they have previously been treated with pembrolizumab 
15.199c Myocarditis has been reported and associated with pembrolizumab. 
Instruct patients to report chest pain, SOB, or dyspnea to study team immediately 
and/or seek emergency medical attention. 
15.199d Autoimmune hematologic disorders including ITP and hemolytic 
anemia have been reported. Monitor blood counts closely and report any 
abnormalities to the study team. 
15.199e Rare neurologic disorders including Guillian-Barre syndrome and 
myasthenia gravis have been reported. Instruct patients to report any neurologic 
symptoms including weakness, parasthesias or numbness, tingling to the study 
team immedicately. 

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16.0 
Statistical Considerations and Methodology 
16.1 
Overview 
This is a phase II study designed to assess the overall cutaneous response rate at cycle 9 
in MF patients treated with pembrolizumab. It is a single one-stage design with an 
interim analysis based on the Simon optimal design with 85% power and 10% Type I 
error. 
 
NOTE: As per Amendment 4, accrual will cease after the enrollment of 10 patients due 
to sponsor decision on funding.  Thus, the study power and type I error will not be 
appropriate for the analysis, as the study will not be able to go to full accrual.  The study 
will be analyzed at the pre-defined interim step. 
 
16.11 Endpoint: 
The primary endpoint is overall cutaneous response (cutaneous complete 
response (CR), cutaneous 90 response (CR90) or cutaneous partial response 
(PR)) as defined using the mSWAT score as stated in section 11.0. Throughout 
Section 16.0, CR, CR90 or PR will be considered synonymous with “success”, 
unless specified otherwise. All patients meeting the eligibility criteria who have 
signed a consent form and have begun treatment will be evaluable for response. 
 
16.2 
Statistical Design 
16.21 Design: The largest success proportion where the proposed treatment regimen 
would be considered ineffective in this population is 15%, and the smallest 
success proportion that would warrant subsequent studies with the proposed 
regimen in this patient population is 35%. This design uses 28 evaluable patients 
to test the null hypothesis that the true complete response rate is at most 15%. 
16.22 Interim Analysis: Enter 10 evaluable patients to the study. If there are less than 2 
successes in the first 10 evaluable patients, we will consider this regimen 
ineffective in this patient population and terminate this study. Otherwise, if the 
number of successes is at least 2, we will continue accrual. 
16.23 N/A as per Amendment 4: Final Decision rule: If 6 or fewer successes are 
observed in the first 28 evaluable patients, we will consider this regimen 
ineffective in this patient population. Otherwise, if the number of successes is at 
least 7, this will be considered evidence of promising activity and the treatment 
may be recommended for further testing in subsequent studies. 
16.24 N/A as per Amendment 4: NOTE: We will not suspend accrual at the interim 
analysis to allow the first 10 patients to become evaluable, unless undue toxicity 
is observed. Given the limited overall sample size and the inclusion of an 
adverse events stopping rule, we feel it is ethical to not halt accrual for the 
interim analysis. However, if accrual is extremely rapid, we may temporarily 
suspend accrual in order to obtain safety data on these patients before re-opening 
accrual to further patients. 
16.3 
Sample Size, Accrual Rate and Power and Significance Level 
16.31 Sample Size: This study is expected to require a minimum of 10 and a maximum 
of 28 evaluable patients. We anticipate accruing 3 (10%) additional patients to 
account for ineligibility, cancellation, major treatment violation, or other reasons. 
Therefore, the study is expected to accrue a maximum of 31 patients overall.  As 
per Amendment 4, accrual will cease at 10 patients. 
16.32 Accrual Rate and Study Duration: The anticipated accrual rate is 10 evaluable 
patients per year. Therefore, the accrual period is expected to be 3.1 years. The 

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primary endpoint will be evaluated approximately 3.75 years after the trial opens, 
or after the last patient accrued has received 24 months of treatment. 
16.33 Power and Significance Level: Assuming that the number of successes is 
binomially distributed, the significance level is .10, i.e. there is a 10% chance of 
finding the drug to be effective when it truly is not. The probability of declaring 
that this regimen warrants further study (i.e. statistical power) under various 

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success proportions and the probability of stopping accrual after the interim 
analysis can be tabulated as a function of the true success proportion. 
If the true success proportion is... 
0.15 
0.20 
0.25 
0.30 
0.35 
Then the probability of declaring 
that the regimen warrants further 
study is… 
0.456 
0.624 
0.756 
0.851 
0.914 
and the probability of stopping after 
the interim analysis is … 
0.544 
0.376 
0.244 
0.149 
0.086 
16.34 Other considerations: Adverse events, quality/duration of response, and patterns 
of treatment failure observed in this study, as well as scientific discoveries or 
changes in standard care will be taken into account in any decision to terminate 
the study. 
 
16.4 
Analysis Plan 
16.41 Primary Outcome Analysis: The mSWAT score at baseline and cycle 9 will be 
used for change in baseline calculations. All calculated values will use the last- 
observation-carried forward for any participants who withdraw, are lost to follow 
up, or exit the study per protocol. The proportion of successes will be estimated 
by the number of successes divided by the total number of evaluable patients will 
be analysed using Mann–Whitney U for nonparametric data and the student t- 
test. Confidence intervals for the true success proportion will be calculated 
according to the approach of Duffy and Santner (Duffy D 1987). 
 
16.42 Secondary Outcome Analysis: These analyses will include all patients meeting 
the eligibility criteria who have signed a consent form and have begun treatment, 
including patients who fail to achieve a complete or partial response. 
 
Adverse Events: All eligible patients that have initiated treatment will be 
considered evaluable for assessing adverse event rate(s). The maximum grade 
for each type of adverse event will be recorded for each patient, and frequency 
tables will be reviewed to determine patterns. Additionally, the relationship of 
the adverse event(s) to the study treatment will be taken into consideration. 
 
Response Rates: 
Changes in mSWAT scores from baseline will be evaluated at cycle 9. 
Summary statistics will be calculated. 
 
Patients will be assigned response based on the mSWAT criteria in 
section 11.0. Proportions of patients will be calculated and described 
using summary statistics. Proportions of interest are patients having 
CR, CR90 and PR; patients having stable subcutaneous disease; 
patients having progressive cutaneous disease; and patients having an 
overall systemic response rate. 
Progression free survival time is defined for all evaluable patients as the time 
from registration to relapse or death due to any cause. Patients are censored if 
they have not achieved a progression at the time of analysis. The distribution of 
progression-free survival will be estimated using the method of Kaplan-Meier. 
In addition, the progression-free survival rate at 5 years after registration will be 
reported. 

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Duration of response is defined for all evaluable patients who have 
achieved a CR, CR90 or PR as the date at which the patient’s objective 
status is first noted to be a CR, CR90 or PR to the earliest date relapse 
is documented. The distribution of duration of complete response will 
be estimated using the method of Kaplan-Meier. 
Time to response is defined as the time from registration to CR, CR90 
or PR. The distribution of survival time will be estimated using the 
method of Kaplan-Meier (Kaplan and Meier 1958). 
Overall survival time is defined as the time from registration to death 
due to any cause. Patients are censored if they are alive at the time of 
analysis. The distribution of survival time will be estimated using the 
method of Kaplan-Meier (Kaplan and Meier 1958). In addition, the 
overall survival rate at 2 years after registration will be reported. 
Additional Analyses: All endpoints may be analysed using patient 
characteristics to explore possible associations of demographics with 
the endpoints. Possible characteristics include clinical stage, gender 
and prior treatments. 
 
16.43 Correlative Analyses 
Immunohistochemistry will be used to quantify levels of CD4, CD8, PD- 
1/CD279, and PD- L1 expression before and after treatment with pembrolizumab 
and will be used for change in baseline calculations at baseline and end of cycle 
2. Qualitative measures of the strength of PD-1 and PD-L1 expression will use 
published standardized grading scales for categorical classification purposes. 
 
16.5 
Primary Endpoint Completion Date for 
 Reporting 
For purpose of 
reporting, the Primary Endpoint Completion Date 
(PECD) for this study is the time the last patient registered has been followed for at least 
7 months. 
 
16.6 
Data Safety and Monitoring 
16.61 The study statistician will review the study weekly to monitor accrual, endpoints 
and adverse events. Additionally, the Mayo Clinic Cancer Center (MCCC) Data 
Safety Monitoring Board (DSMB) is responsible for reviewing accrual and safety 
data for this trial at least twice a year, based on reports provided by the MCCC 
Statistical Office. 
16.62 This study will be monitored by the Clinical Data Update System (CDUS) 
version 2.0. A full report containing cumulative CDUS data will be submitted 
quarterly to CTEP by electronic means. Reporting time points are: January 31, 
April 30, July 31, and October 31. 
16.63 Adverse Event Stopping Rules: The stopping rules specified below are based on 
the knowledge available at study development. We note that the Adverse Event 
Stopping Rule may be adjusted in the event of either (1) the study re-opening to 
accrual or (2) at any time during the conduct of the trial and in consideration of 
newly acquired information regarding the adverse event profile of the 
treatment(s) under investigation. The study team may choose to suspend accrual 

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because of unexpected adverse event profiles that have not crossed the specified 
rule below. 
Accrual will be temporarily suspended to this study if at any time we observe 
events considered at least possibly related to study treatment (i.e. an adverse 
event with attribute specified as “possible,” “probable,” or “definite”) that satisfy 
one of the following: 
• 
if 2 or more patients in the first 10 treated patients (20%) experience a grade 
4 or higher non-hematologic adverse event at least possibly related to 
treatment. 
• 
if after the first 10 patients have been treated, 20% of all patients experience 
a grade 4 or higher non-hematologic adverse event at least possibly related to 
treatment. 
We note that we will review grade 4 and 5 adverse events deemed “unrelated” or 
“unlikely to be related”, to verify their attribution and to monitor the emergence 
of a previously unrecognized treatment-related adverse event. 
 
16.63 Accrual Stopping Rule 
The study design assumes that 2 patients will accrue per month, leading to a 26-month 
total accrual. At 6 months, if the total accrual is below 50% of the expected (fewer than 6 
patients) then the significance and power will be much better than designed for and a 
sample size reduction may be called for. Consequently, we will update the design and 
may adjust sample size and/or duration of follow-up. At 6 months, if the total accrual is 
above 200% (more than 24 patients) then we may have lost significance and/or power 
and an increase in sample size or a lengthening of total observation time may be 
necessary. Consequently, we may pause accrual or update the design and may adjust the 
sample size to achieve the desired significance and power. 
 
16.7 
Inclusion of Women and Minorities 
16.71 This study will be available to all eligible patients, regardless of race, gender, or 
ethnic origin. 
16.72 There is no information currently available regarding differential effects of this 
regimen in subsets defined by race, or ethnicity, and there is no reason to expect 
such differences to exist. Therefore, although the planned analysis will, as 
always, look for differences in treatment effect based on race, the sample size is 
not increased in order to provide additional power for subset analyses. 
16.73 The geographical region served by MCCC has a population which includes 
approximately 3% minorities. Based on prior MCCC studies involving similar 
disease sites, we expect about 3-5% of patients will be classified as minorities by 
race and about 30% of patients will be women. Expected sizes of racial by 
gender subsets are shown in the following table: 
Accrual Estimates by Gender/Ethnicity/Race 
Ethnic Category 
Sex/Gender 
Females 
Males 
Unknown 
Total 
Hispanic or Latino 
5 
4 
0 
9 
Not Hispanic or Latino 
11 
11 
0 
22 

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Protocol Version Date: 30NOV2022  
 
 
 
 
Ethnic Category 
Sex/Gender 
Females 
Males 
Unknown 
Total 
Ethnic Category: Total of all subjects 
16 
15 
0 
31 
Racial Category 
American Indian or Alaskan Native 
0 
0 
0 
0 
Asian 
0 
0 
0 
0 
Black or African American 
4 
5 
0 
9 
Native Hawaiian or other Pacific Islander 
0 
0 
0 
0 
White 
12 
10 
0 
22 
Racial Category: Total of all subjects 
16 
15 
0 
31 
 
 
 
Ethnic 
Categories: 
Hispanic or Latino – a person of Cuban, Mexican, Puerto Rico, South or Central 
American, or other Spanish culture or origin, regardless of race. The term “Spanish 
origin” can also be used in addition to “Hispanic or Latino.” 
Not Hispanic or Latino 
Racial 
Categories: 
American Indian or Alaskan Native – a person having origins in any of the original 
peoples of North, Central, or South America, and who maintains tribal affiliations or 
community attachment. 
Asian – a person having origins in any of the original peoples of the Far East, 
Southeast Asia, or the Indian subcontinent including, for example, Cambodia, China, 
India, Japan, Korea, Malaysia, Pakistan, the Philippine Islands, Thailand, and 
Vietnam. (Note: Individuals from the Philippine Islands have been recorded as Pacific 
Islanders in previous data collection strategies.) 
Black or African American – a person having origins in any of the black racial 
groups of Africa. Terms such as “Haitian” or “Negro” can be used in addition to 
“Black or African American.” 
Native Hawaiian or other Pacific Islander – a person having origins in any of the 
original peoples of Hawaii, Guam, Samoa, or other Pacific Islands. 
White – a person having origins in any of the original peoples of Europe, the Middle 
East, or North Africa. 

Protocol Version Date:  17May2022 
 
 
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57 
17.0 
Pathology Considerations/Tissue Biospecimens 
17.1 
Summary Table of Research Tissue Specimens to be collected for this Protocol 
 
Research Study 
(Section for more 
information) 
Specimen 
Purpose 
(check all 
that apply) 
Mandatory 
or Optional 
Type of 
Tissue to 
Collect 
Block, Slides, 
Core, etc. (# of 
each to 
submit) 
After 
registration 
Cycle 2 
Day 15 
Process 
at site? 
(Yes or 
No) 
Histopathologic and 
immunohistochemical 
analysis 
☒ 
Correlative 
☐ Eligibility 
Confirmation 
☐ Banking 
☐ Other 
(specify) 
Mandatory 
FFPE 
H&E Slides 
and 4- 
unstained 
slides of 5 
microns 
X 
X 
Yes 

 
MC1788 
 
 
17.2 
Diagnostic Slides from Original and /or Recurrent Tissue 
Prior to the initial dose of pembrolizumab, a 6 mm punch skin biopsy of the most 
common presenting morphology (i.e. patch, plaque, or tumor) will be obtained for each 
study participant; at Cycle 2, Day 15, an additional 6 mm punch skin biopsy of the same 
morphologic type will be obtained. 
 
Please see the number of required unstained slides for each test in the table. Slides should 
be sent to BAP lab in Jacksonville 
 
 
 
17.3 
Correlative Tissue Collection 
17.31 Tissue Kits will not be provided for this protocol.. 
17.32 Paraffin Embedded Tissue 
17.321 
Submit H&E as well as uncharged, unstained slides – see table. Do not 
use coverslips, do not bake. 5 micron thick sections on uncharged 
slides at ambient temperature. 
17.4 
Background and Methodology 
17.41 
The use of formalin-fixed paraffin embedded tissue for standard histology is a 
well-established modality in the diagnosis of treatment of cutaneous lymphoma. 
Histologic factors such as epidermotropism, the extensive of dermal involvement, 
and cytomorphologic features are all of import. Immunohistochemistry is 
additionally routinely utilized in classifying the nature of the atypical mononuclear 
infiltrate and in the assessment of large cell transformation. Histopathology will be 
used for diagnostic confirmation and to assess for evidence of histologic regression 
of tumor with treatment. Immunohistochemistry will be used to quantify levels of 
CD4, CD8, PD-1/CD279, and PD-L1 expression before and after treatment with 
pembrolizumab and will be used for change in baseline calculations at after 
registration and Cycle 2, Day 15. Qualitative measures of the strength of PD-1 and 
PD-L1 expression will use published standardized grading scales for categorical 
classification purposes. 
 
 
 
 
 
 
 
 
 
Protocol version: 17May2022 

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Protocol Version Date:17May2022 
 
 
 
 
18.0 
Records and Data Collection Procedures 
18.1 
Submission Timetable 
Data submission instructions for this study can be found in the Data Submission 
Schedule. 
18.2 
Survival Follow-up 
See Section 4. 
18.3 
CRF completion 
This study will use Medidata Rave for remote data capture (rdc) of all study data. Data 
collection for this study will be done exclusively through the Medidata Rave clinical data 
management system. Access to the trial in Rave is granted through the iMedidata 
application to all persons with the appropriate roles assigned in Regulatory Support 
System (RSS). To access Rave via iMedidata, the site user must have an active account 
and the appropriate Rave role (Rave CRA, Read-Only, Site Investigator) on either the 
organization roster at the enrolling site. 
18.4 
Site responsibilities 
Each site will be responsible for insuring that all materials contain the patient’s initials, 
MCCC registration number, and MCCC protocol number. Patient’s name must be 
removed. 
18.5 
Supporting documentation 
This study requires supporting documentation for diagnosis and progression prior to 
study entry as well as for evidence of response to study therapy and progression after 
study therapy. 
 
Supporting documentation for diagnosis will include a pathology report from the most 
recent tumor tissue biopsy, dermatology exam clinical note, imaging report, and T & B- 
cell Quantitation lab report, if blood involved by tumor. These documents should be 
uploaded into the Supporting Documentation: Baseline form in the Medidata Rave 
system within 14 days of registration. 
 
For response to treatment, supporting documentation includes a dermatology exam 
clinical note, imaging report, and T & B-cell Quantitation lab report, if blood involved 
with tumor. 
 
For patients who progress, supporting documentation of all sites of progression is 
required and can include dermatology exam clinical note, imaging report, or T & B-cell 
Quantitation lab report, if blood involved with tumor. 
 
18.6 
Labeling of materials 
Each site will be responsible for insuring that all materials contain the patient’s initials, 
MCCC registration number, and MCCC protocol number. Patient’s name must be 
removed. 
18.7 
Overdue lists 

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Protocol Version Date:17May2022 
 
 
 
 
 
 
 
19.0 
Budget 
 
A list of overdue forms and outstanding queries will be available in Rave through the 
Rave Task Summary. In addition to this, the Overdue Materials report is available on the 
Cancer Center Systems homepage. 
 
19.1 
Costs charged to patient: routine clinical care 
19.2 
Tests to be research funded: Tumor Biopsy at Cycle 2, Day 15, Dermatology exam, 
Standardized Clinical photography, T and B-cell Quantitation after Cycle 4 during course 
of treatment and at the End of Treatment Visit, and research tissue. Drug provided free of 
charge. 
19.3 
Other budget concerns: 
Merck will provide Mayo Clinic with funding to support the costs of running this study. 

MC1788 
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Protocol Version Date:17May2022 
 
 
 
 
20.0 
References 
1. Devata, S. and R. A. Wilcox (2016). Cutaneous T-Cell Lymphoma: A Review with a Focus on 
Targeted Agents. American Journal of Clinical Dermatology, 17(3): 225-2377. 
2. Khodadoust, M., et al. (2016). Pembrolizumab for Treatment of Relapsed/Refractory Mycosis 
Fungoides and Sezary Syndrome: Clinical Efficacy in a Citn Multicenter Phase 2 Study. Blood, 
128(22): 181-181. 
3. Nguyen, G. H., et al. (2017). Upregulation of inhibitory signaling receptor programmed death 
marker-1 (PD-1) in disease evolution from cutaneous lymphoid dyscrasias to mycosis fungoides 
and Sezary's syndrome. Annals Diagnostic Pathology, 28: 54-59. 
4. Oken, M.M., et al., 1982. Toxicity and response criteria of the eastern cooperative oncology 
group. American Journal of Clinical Oncology, 5:649-655, 1982. 
5. Olsen, E. A., et al. (2011). Clinical end points and response criteria in mycosis fungoides and 
Sezary syndrome: a consensus statement of the International Society for Cutaneous Lymphomas, 
the United States Cutaneous Lymphoma Consortium, and the Cutaneous Lymphoma Task Force 
of the European Organisation for Research and Treatment of Cancer. Journal of Clinical 
Oncology, 29(18): 2598-26 
6. Phillips, T., et al. (2016). Challenges and opportunities for checkpoint blockade in T-cell 
lymphoproliferative disorders. Journal for ImmunoTherapy of Cancer, 4: 95. 
7. Rozati, S. and Y. H. Kim (2016). Experimental treatment strategies in primary cutaneous T-cell 
lymphomas. Current Opinion in Oncology, 28(2): 166-171. 
8. Trautinger, F., et al. (2017). European Organisation for Research and Treatment of Cancer 
consensus recommendations for the treatment of mycosis fungoides/Sezary syndrome - Update 
2017. European Journal of Cancer, 77: 57-74. 
9. Wang, Y., et al. (2018). PD-1-PD-L1 immune-checkpoint blockade in malignant lymphomas. 
Annals of Hematology, 97(2): 229-237. 
10. Warren, S., et al. (2017). Unrelated immunodeficiency states may impact outcomes and immune 
checkpoint molecule expression in patients with mycosis fungoides: A clinicopathologic case- 
control study. Journal of the American Academy of Dermatology, 78(3) 530-539. 
11. Wilcox, R. A. (2017). Cutaneous T-cell lymphoma: 2017 update on diagnosis, risk-stratification, 
and management. American Journal of Hematology, 92(10): 1085-1102. 

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Protocol Version Date:17May2022 
 
 
 
 
Appendix I 
ECOG Performance Status 
 
 
ECOG PERFORMANCE STATUS* 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out 
work of a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all selfcare but unable to carry out any work 
activities. Up and about more than 50% of waking hours 
3 
Capable of only limited selfcare, confined to bed or chair more than 50% of 
waking hours. 
4 
Completely disabled. Cannot carry on any selfcare. Totally confined to bed or 
chair. 
5 
Dead 
*As published in Am. J. Clin. Oncol.: 
Oken, M.M., Creech, R.H., Tormey, D.C., Horton, J., Davis, T.E., McFadden, E.T., Carbone, P.P.: 
Toxicity And Response Criteria Of The Eastern Cooperative Oncology Group. Am J Clin Oncol 5:649- 
655, 1982. 
 
The ECOG Performance Status is in the public domain therefore available for public use. To duplicate the 
scale, please cite the reference above and credit the Eastern Cooperative Oncology Group, Robert Comis 
M.D., Group Chair. 
 
From