Pembrolizumab in Treating Patients With Relapsed or Refractory Stage IB-IVB Mycosis Fungoides or Sezary Syndrome

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02243579
• Collaborator: (none)
• Enrollment: 24
• Locations: 8
• Arm: 1
• Actual Duration (Months): 53.5
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial studies how well pembrolizumab works in treating patients with stage IB-IVB mycosis fungoides or Sezary syndrome that has returned after a period of improvement or has not responded to at least one type of treatment. Monoclonal antibodies, such as pembrolizumab, may block cancer growth in different ways by targeting certain cells.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Mycosis Fungoides and Sezary Syndrome; Refractory Mycosis Fungoides and Sezary Syndrome; Stage IB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IIIB Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVA Mycosis Fungoides and Sezary Syndrome AJCC v7; Stage IVB Mycosis Fungoides and Sezary Syndrome AJCC v7	Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To assess the response rate of MK-3475 (pembrolizumab) in subjects with relapsed/refractory mycosis fungoides/Sezary syndrome (MF/SS).

SECONDARY OBJECTIVES:

1. To explore the clinical activity of MK-3475 in subjects with relapsed/refractory MF and SS with respect to the following endpoints: duration of response (DOR); progression-free survival (PFS); overall survival (OS).

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving complete response [CR]) in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 12 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of MK-3475 for the Treatment of Relapsed/Refractory Mycosis Fungoides/Sezary Syndrome
• Actual Study Start Date: Oct 15, 2014
• Actual Primary Completion Date: Jan 4, 2018
• Actual Study Completion Date: Apr 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (pembrolizumab) Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Pembrolizumab; Given IV; Other Names: Keytruda Lambrolizumab MK-3475 SCH 900475

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome [Up to 3.2 years]

   A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes.

Secondary Outcome Measures

1. Duration of Response [The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks]

   Was estimated using the Kaplan-Meier method (Duration of Response Probability).

2. Progression Free Survival (PFS) [The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks]

   Was estimated using the Kaplan-Meier method (Progression Free Survival Probability).

3. Overall Survival (OS) [The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks]

   Was estimated using the Kaplan-Meier method (Overall Survival Probability).

4. Time to Onset of First Drug-related Toxicity [Up to 4 years]

   Summary statistics (mean and SD) for time to onset of first drug-related toxicity was provided.

5. Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0 [Up to 4 years]

   Adverse events were summarized as counts and frequencies by toxicity grade.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• This trial will include subjects with stage IB-IVB MF/SS (maximal stage since diagnosis will determine eligibility), and who have relapsed, are refractory, or progressed after at least one standard systemic therapy; current disease stage at time of entry will also be documented but will not be used for eligibility

• Subjects must have the following minimum wash-out and adverse event (AE) recovery period from previous treatments without treatment between documentation of relapse/progression and enrollment of specifically:

• = 2 weeks for local radiation therapy

• = 4 weeks for systemic cytotoxic anticancer agents, anticancer investigational agents that are not defined as immunotherapy, or for tumor-targeting monoclonal antibodies (mAbs) with the exception of alemtuzumab for which the washout is at least 8 weeks

• = 15 weeks for anti-cluster of differentiation (CD)137 or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)

• = 2 weeks from resolution (i.e., =< grade 1 or at baseline) from AEs due to procedures performed or therapeutic agents administered

• = 2 weeks for retinoids, interferons, vorinostat, romidepsin, denileukin diftitox, and therapeutic doses of oral corticosteroids (physiologic replacement doses of oral corticosteroids are allowed, topical corticosteroids are allowed)

• = 2 weeks for phototherapy

• = 1 week for topical therapy (including retinoid, nitrogen mustard, or imiquimod)

• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale

• Life expectancy of at least 6 months

• Performed within 10 days of treatment initiation: Leukocytes >= 2,000/mcL

• Performed within 10 days of treatment initiation: Absolute neutrophil count >= 1,500/mcL

• Performed within 10 days of treatment initiation: Platelets >= 100,000/mcL

• Performed within 10 days of treatment initiation: Hemoglobin >= 9 g/dL OR >= 5.6 mmol/L

• Performed within 10 days of treatment initiation: Serum total bilirubin =< 1.5 x upper limit of normal (ULN) OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN

• Performed within 10 days of treatment initiation: Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for patients with liver metastases

• Performed within 10 days of treatment initiation: Serum creatinine =< 1.5 x ULN OR measured or calculated creatinine clearance >= 60 mL/min for subject with creatinine clearance (CrCl) levels > 1.5 x institutional ULN (glomerular filtration rate [GFR] can also be used in place of creatinine or CrCl)

• Performed within 10 days of treatment initiation: International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy in which case the INR or PT must be within the therapeutic range of intended use for the anticoagulant

• Performed within 10 days of treatment initiation: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN unless subject is receiving anticoagulant therapy in which case the aPTT must be within the therapeutic range of intended use for the anticoagulant

• Performed within 10 days of treatment initiation: Thyroid stimulating hormone (TSH) within institutional limits (ie: normal); if TSH is greater or less than institutional limits patients may participate if their thyroxine (T4) is within normal limits (WNL); patients may be on a stable dose of replacement thyroid medication; dose adjustments are allowed if needed

• Patients must provide tissue from a punch biopsy of the skin at baseline, at the time of a clinical event (at the time of response, progression or appearance of a new lesion) and at the end of treatment; additional punch biopsies every 3 cycles are optional; an archival tissue sample is optional

• Have measurable disease based on modified severity-weighted assessment tool (mSWAT); tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions

• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication

• Female patients of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required

• Female patients of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication; patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year

• Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MK-3475 administration

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients who have had chemotherapy or targeted small molecule therapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier

• Note: patients with =< grade 2 neuropathy are an exception to this criterion and may qualify for the study

• Note: if patients received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy

• Patients who are currently participating in or have participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment

• Has a diagnosis of immunodeficiency or is receiving therapeutic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment

• Has had a prior monoclonal antibody within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from AEs due to agents administered more than 4 weeks earlier

• Has a known additional malignancy that is progressing or requires active treatment; exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy

• Patients with known brain metastases should be excluded from this clinical trial

• Patients with carcinomatous meningitis should also be excluded

• Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-3475

• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; patients with vitiligo or resolved childhood asthma/atopy would be an exception to this rule; patients that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study; the use of physiologic doses of corticosteroids may be approved after consultation with the protocol principal investigator (PI) and Cancer Immunotherapy Trials Network (CITN); patients with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study

• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator

• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial

• Has received prior therapy with an anti-programmed cell death (PD)-1, anti-PD-ligand (L)1, anti-PD-L2

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, interstitial lung disease or active, non-infectious pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• History of other pulmonary disease such as emphysema or chronic obstructive pulmonary disease, (forced expiratory volume in one second [FEV1] < 60% of predicted for height and age); pulmonary function tests (PFTs) are required in patients with prolonged smoking history or symptoms of respiratory dysfunction

• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-study visit through 120 days after the last dose of trial treatment; breastfeeding should be discontinued if the mother is treated with MK-3475

• Men and non-pregnant, non-breast-feeding women may be enrolled if they are willing to use 2 methods of birth control or are considered highly unlikely to conceive; highly unlikely to conceive is defined as 1) surgically sterilized, or

1. postmenopausal (a woman who is >= 45 years of age and has not had menses for greater than 1 year will be considered postmenopausal), or 3) not heterosexually active for the duration of the study; the two birth control methods can be barrier method or a barrier method plus a hormonal method to prevent pregnancy; patients should start using birth control from the time of the pre-study visit, through the course of the study and for 120 days after the last dose of study medication; the following are considered adequate barrier methods of contraception: diaphragm, condom (by the partner), copper intrauterine device, sponge, or spermicide; appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents)

• Patients 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 they must adhere to the contraception requirement (described above) for the duration of the study and during the follow-up period; if there is any question that a patient will not reliably comply with the requirements for contraception, that patient should not be entered into the study

• If a patient inadvertently becomes pregnant while on treatment with MK-3475, 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 without delay and within 24 hours 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 patient impregnates his female partner the study personnel at the site must be informed immediately and the pregnancy reported and followed

• Patients who are human immunodeficiency virus (HIV) positive may participate IF they meet the following eligibility requirements:

• They must be stable on their anti-retroviral regimen, and they must be healthy from an HIV perspective

• They must have a CD4 count of greater than 250 cells/mcL

• They must not be receiving prophylactic therapy for an opportunistic infection

• Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is detected)

• Has received a live vaccine within 30 days prior to the first dose of trial treatment

• Has a known human T-lymphotropic virus type 1 (HTLV) infection

• Patient has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Institute Palo Alto	Palo Alto	California	United States	94304
2	Yale University	New Haven	Connecticut	United States	06520
3	Moffitt Cancer Center	Tampa	Florida	United States	33612
4	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
5	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
6	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
7	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
8	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Youn Kim, Cancer Immunotherapy Trials Network

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 8, 2018

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT02243579
• Other Study ID Numbers: NCI-2014-00709; NCI-2014-00709; CITN-10; CITN-10; P30CA015704; U01CA154967
• First Posted: Sep 18, 2014
• Last Update Posted: Sep 20, 2019
• Last Verified: Aug 1, 2019

• Additional relevant MeSH terms: Mycoses; Mycosis Fungoides; Sezary Syndrome; Syndrome; Pembrolizumab

Study Results

Participant Flow

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Period Title: Overall Study
STARTED	24
COMPLETED	4
NOT COMPLETED	20

Baseline Characteristics

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Overall Participants	24
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 37.5%
>=65 years	15 62.5%
Sex: Female, Male (Count of Participants)
Female	6 25%
Male	18 75%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	3 12.5%
White	20 83.3%
More than one race	0 0%
Unknown or Not Reported	1 4.2%
Region of Enrollment (participants) [Number]
United States	24 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR), Defined as a Confirmed Partial Response (PR) or Complete Response (CR) Using Global Assessment Standard Response Criteria for Mycosis Fungoides and Sezary Syndrome
Description	A generalized linear model for the objective response rate used a binominal error distribution. The model included as covariates all available baseline predictors of the missing outcomes.
Time Frame	Up to 3.2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	24
Confirmed Complete Response	2 8.3%
Confirmed Partial Response	7 29.2%
Stable Disease	9 37.5%
Progressive Disease	6 25%

2. Secondary Outcome

Title	Duration of Response
Description	Was estimated using the Kaplan-Meier method (Duration of Response Probability).
Time Frame	The time interval between the date of first response (CR/PR) and the date of progression as assessed by standard Mycosis Fungoides and Sezary Syndrome response criteria, assessed at 26 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	9
26 weeks	1.0
52 weeks	0.8571

3. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	Was estimated using the Kaplan-Meier method (Progression Free Survival Probability).
Time Frame	The time from allocation to the first documented disease progression or death due to any cause, whichever occurs first, assessed at 26 and 52 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	24
26 weeks	0.7380
52 weeks	0.6457

4. Secondary Outcome

Title	Overall Survival (OS)
Description	Was estimated using the Kaplan-Meier method (Overall Survival Probability).
Time Frame	The time from randomization to death due to any cause, assessed at 52, 104 and 156 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	24
52 weeks	0.95
104 weeks	0.7917
156 weeks	0.5429

5. Secondary Outcome

Title	Time to Onset of First Drug-related Toxicity
Description	Summary statistics (mean and SD) for time to onset of first drug-related toxicity was provided.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

Patients with drug-related toxicities included in the analysis

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	22
Mean (Standard Deviation) [Days]	64.5 (121.3)

6. Secondary Outcome

Title	Incidence of Adverse Events Graded Using the Common Terminology Criteria for Adverse Events Version 5.0
Description	Adverse events were summarized as counts and frequencies by toxicity grade.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
Measure Participants	24
Maximum Toxicity Grade 1	2 8.3%
Maximum Toxicity Grade 2	7 29.2%
Maximum Toxicity Grade 3	9 37.5%
Maximum Toxicity Grade 4	6 25%

Adverse Events

Time Frame	Up to 4 years
Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for up to 2 years (6 months for patients achieving CR) in the absence of disease progression or unacceptable toxicity. Laboratory Biomarker Analysis: Correlative studies Pembrolizumab: Given IV
All Cause Mortality
	Treatment (Pembrolizumab)
	Affected / at Risk (%)	# Events
Total	7/24 (29.2%)
Serious Adverse Events
	Treatment (Pembrolizumab)
	Affected / at Risk (%)	# Events
Total	11/24 (45.8%)
Cardiac disorders
Atrial Fibrillation	1/24 (4.2%)
Heart Failure	1/24 (4.2%)
Eye disorders
Corneal Ulcer	1/24 (4.2%)
Periorbital Edema	1/24 (4.2%)
Gastrointestinal disorders
Colitis	1/24 (4.2%)
Colonic obstruction	1/24 (4.2%)
Duodenitis	1/24 (4.2%)
General disorders
Edema face	1/24 (4.2%)
Fatigue	1/24 (4.2%)
Immune system disorders
Anaphylaxis	1/24 (4.2%)
Infections and infestations
Lung Infection	1/24 (4.2%)
Sepsis	1/24 (4.2%)
Urinary Tract Infection	2/24 (8.3%)
Investigations
Alanine Aminotransferase increased	1/24 (4.2%)
Aspartate Aminotransferase increased	1/24 (4.2%)
Metabolism and nutrition disorders
Hyperuricemia	1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/24 (4.2%)
Psychiatric disorders
Confusion	1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/24 (4.2%)
Hypoxia	1/24 (4.2%)
Pneuminitis	1/24 (4.2%)
Pulmonary Edema	1/24 (4.2%)
Vascular disorders
Hypertension	1/24 (4.2%)
Other (Not Including Serious) Adverse Events
	Treatment (Pembrolizumab)
	Affected / at Risk (%)	# Events
Total	24/24 (100%)
Blood and lymphatic system disorders
Anemia	7/24 (29.2%)
Low Hemoglobin	1/24 (4.2%)
Ear and labyrinth disorders
Vertigo	2/24 (8.3%)
Eye disorders
Blurred Vision	1/24 (4.2%)
Keratitis	1/24 (4.2%)
Gastrointestinal disorders
Abdominal Pain	1/24 (4.2%)
Colonic hemorrhage	1/24 (4.2%)
Constipation	1/24 (4.2%)
Diarrhea	3/24 (12.5%)
Nausia	2/24 (8.3%)
Vomiting	1/24 (4.2%)
General disorders
Chills	1/24 (4.2%)
Edema face	2/24 (8.3%)
Edema limbs	4/24 (16.7%)
Edema trunk	1/24 (4.2%)
Fatigue	7/24 (29.2%)
Fever	2/24 (8.3%)
Weakness	1/24 (4.2%)
Weakness (grade decrease)	1/24 (4.2%)
Firm tender lump on his left lateral thigh, no trauma to the area	1/24 (4.2%)
Generalized edema	1/24 (4.2%)
Malaise	1/24 (4.2%)
Pain	1/24 (4.2%)
Immune system disorders
Inflammation/Flare reaction	1/24 (4.2%)
Infections and infestations
Conjunctivitis	1/24 (4.2%)
Esophageal infection	1/24 (4.2%)
Eye infection	1/24 (4.2%)
Infection S/P scheduled Mohs surgery	1/24 (4.2%)
Right lower leg infection related to approved radiation and wound care	1/24 (4.2%)
Mucosal infection (thrush)	1/24 (4.2%)
Mucosal infection - thrush	1/24 (4.2%)
Upper eyelid infection	1/24 (4.2%)
otitis externa	1/24 (4.2%)
rash pustular	1/24 (4.2%)
Skin infection	2/24 (8.3%)
Soft tissue infection	1/24 (4.2%)
Upper respiratory infection	1/24 (4.2%)
Urinary tract infection	1/24 (4.2%)
Injury, poisoning and procedural complications
Fall	1/24 (4.2%)
Infusion related reaction	2/24 (8.3%)
Investigations
Alanine aminotransferase increased	2/24 (8.3%)
Alkaline phosphatase inceased	1/24 (4.2%)
Aspartate aminotransferase increased	2/24 (8.3%)
Blood bilirubin increased	2/24 (8.3%)
Cardiac troponin T increased	1/24 (4.2%)
Creatinine increased	4/24 (16.7%)
Investigations	1/24 (4.2%)
Lymphocyte count decreased	1/24 (4.2%)
Neutrophil count decreased	1/24 (4.2%)
Weight gain	1/24 (4.2%)
Weight loss	2/24 (8.3%)
white blood cell decreased	1/24 (4.2%)
Metabolism and nutrition disorders
Hyperglycemia	6/24 (25%)
Hyperkalemia	1/24 (4.2%)
Hyperuricemia	5/24 (20.8%)
Hypoalbuminemia	2/24 (8.3%)
Hypocalcemia	5/24 (20.8%)
Hypokalemia	1/24 (4.2%)
Hyponatremia	2/24 (8.3%)
Hypophosphatemia	1/24 (4.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/24 (12.5%)
Arthritis	1/24 (4.2%)
Back pain	2/24 (8.3%)
Muscle weakness lower limb	1/24 (4.2%)
Herniated disc	1/24 (4.2%)
neck pain	1/24 (4.2%)
Pain in extremity	3/24 (12.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
BCC right leg	1/24 (4.2%)
SCC forehead	1/24 (4.2%)
Nervous system disorders
Ataxia	1/24 (4.2%)
Syncope	1/24 (4.2%)
Tremor	1/24 (4.2%)
Psychiatric disorders
Anxiety	1/24 (4.2%)
Confusion	3/24 (12.5%)
Insomnia	2/24 (8.3%)
Renal and urinary disorders
Nephrolithiasis	1/24 (4.2%)
Acute kidney injury	1/24 (4.2%)
Reproductive system and breast disorders
Horseness	1/24 (4.2%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	1/24 (4.2%)
Cough	4/24 (16.7%)
Dyspnea	1/24 (4.2%)
Hypoxia	2/24 (8.3%)
Pneumonitis	1/24 (4.2%)
Postnasal drip	1/24 (4.2%)
Bilateral pulmonary infiltrates	1/24 (4.2%)
Sinus inflammation	1/24 (4.2%)
Skin and subcutaneous tissue disorders
Alopecia	3/24 (12.5%)
Dry skin	1/24 (4.2%)
Erythroderma	3/24 (12.5%)
Hyperhidrosis	1/24 (4.2%)
Pruritus	5/24 (20.8%)
Rash maculo-papular	1/24 (4.2%)
Skin eruption/flare, rash	1/24 (4.2%)
immune mediated flare reaction on the face	1/24 (4.2%)
pustular rash	1/24 (4.2%)
Mild skin peeling	1/24 (4.2%)
Erythroderma	1/24 (4.2%)
Night sweats	1/24 (4.2%)
Skin flare	1/24 (4.2%)
Excess skin peeling	1/24 (4.2%)
Urticaria	1/24 (4.2%)
Surgical and medical procedures
Scheduled Mohs surgery	1/24 (4.2%)
Vascular disorders
Hot flashes	1/24 (4.2%)
Hypertension	1/24 (4.2%)
Hypotension	1/24 (4.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.