Pembrolizumab in Treating Patients With Advanced Merkel Cell Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT02267603

Recruitment Status : Completed

First Posted : October 17, 2014

Results First Posted : March 1, 2019

Last Update Posted : July 5, 2023

View this study on the modernized ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

National Cancer Institute (NCI)

Study Type	Interventional
Study Design	Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Recurrent Merkel Cell Carcinoma Stage III Merkel Cell Carcinoma AJCC v7 Stage IIIA Merkel Cell Carcinoma AJCC v7 Stage IIIB Merkel Cell Carcinoma AJCC v7 Stage IV Merkel Cell Carcinoma AJCC v7
Interventions	Other: Laboratory Biomarker Analysis Biological: Pembrolizumab
Enrollment	50

Participant Flow

Recruitment Details	The study was expanded from 24 patients to 50 patients at the request of the pharmaceutical collaborator.
Pre-assignment Details


Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV o...
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity. * NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years. Laboratory Biomarker Analysis: Ancillary studies Pembrolizumab: Given IV
Period Title: Overall Study
Started	50
Completed	6
Not Completed	44

Baseline Characteristics

Arm/Group Title		Treatment (Pembrolizumab)
Arm/Group Description		Patients receive pembrolizumab IV o...
Arm/Group Description		Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity. * NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years. Laboratory Biomarker Analysis: Ancillary studies Pembrolizumab: Given IV
Overall Number of Baseline Participants		50
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Categorical Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	50 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	40 80.0%
	>=65 years	10 20.0%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	50 participants
	Female	16 32.0%
	Male	34 68.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	50 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 2.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	45 90.0%
	More than one race	0 0.0%
	Unknown or Not Reported	4 8.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	50 participants
United States		50

Outcome Measures

1.Primary Outcome


Title	Objective Response Rate (ORR) Defined as the Proportion of Patients Who Have Achieved Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Description	ORR will be estimated as the number of responders as a percent of the ...
Description	ORR will be estimated as the number of responders as a percent of the number of eligible participants who received at least one dose of treatment. If a substantial amount of data is missing, analyses will be performed using parametric generalized linear models fit by maximum likelihood. A generalized linear model for the ORR will use a binomial error distribution. The model will include as covariates all available baseline predictors of the missing outcomes. Responses to continued pembrolizumab will be chronicled and reported.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description:	Patients receive pembrolizumab IV o...
Arm/Group Description:	Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity. * NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years. Laboratory Biomarker Analysis: Ancillary studies Pembrolizumab: Given IV
Overall Number of Participants Analyzed	50
Measure Type: Count of Participants Unit of Measure: Participants
Number participants with partial response (PR)	16 32.0%
Number participants with complete response (CR)	12 24.0%
Combined total participants with either PR or CR	28 56.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Treatment (Pembrolizumab)
	Comments	The protocol was designed w/ a standard Simon 2 stage design. Null hypothesis that true response rate is 5% was tested against a 1-sided alternative. In stage 1, 9 patients were accrued. If no responses in these 9 patients, study was to stop. Otherwise,15 more patients were to be accrued for a total of 24 patients. Study was amended to increase number of patients to 50, following discussion w/ pharmaceutical collaborator and FDA.
	Type of Statistical Test	Other
	Comments	The null hypothesis will be rejected if 3 or more responses are observed in 24 patients. This design yields a type I error rate of 0.10 and power of 0.90 when the true response rate is 25%. Progression-free survival (PFS) at 16 months will be estimated by Kaplan-Meier method. Unless otherwise stated, all statistical tests will be conducted at the α=0.05 (1-sided) level.

Other Statistical Analysis		ORR will be estimated as the # of responders as a % of the # of eligible participants who received at least 1 dose of treatment. If a substantial amount of primary endpoint data are missing (at least 1 value missing from more than 20% of participants), using nonparametric estimation to estimate the ORR requires the missing completely at random assumption may give misleading results. In this case, analyses of the primary endpoint will be performed using parametric generalized linear models fit by maximum likelihood. These methods provide unbiased estimation and inferences under the parametric modeling assumptions and the assumption that the missing data are missing at random (MAR). MAR assumes that the probability of an observation being missing may depend upon the observed responses and upon observed covariates. A generalized linear model for the ORR will use a binomial error distribution. The model will include as covariates all available baseline predictors of the missing outcomes.

2.Secondary Outcome


Title	Progression-free Survival (PFS) Using RECIST 1.1
Description	Survival curves for PFS will be estimated using the Kaplan-Meier metho...
Description	Survival curves for PFS will be estimated using the Kaplan-Meier method. Assessed percentage of participants with progression free survival up to 16 months.
Time Frame	Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 16 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description:	Patients receive pembrolizumab IV o...
Arm/Group Description:	Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity. * NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years. Laboratory Biomarker Analysis: Ancillary studies Pembrolizumab: Given IV
Overall Number of Participants Analyzed	50
Measure Type: Number Unit of Measure: % of participants
	49.9

3.Secondary Outcome


Title	Duration of Response (DOR)
Description	Survival curves for DOR will be estimated using the Kaplan-Meier metho...
Description	Survival curves for DOR will be estimated using the Kaplan-Meier method.
Time Frame	Time interval between the date of first response (CR/PR) and the date of progression, assessed up to 3 years

Outcome Measure Data

Analysis Population Description

Thirty participants with durable response were assessed by RECIST 1.1.


Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description:	Patients receive pembrolizumab IV o...
Arm/Group Description:	Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity. * NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years. Laboratory Biomarker Analysis: Ancillary studies Pembrolizumab: Given IV
Overall Number of Participants Analyzed	30
Median (Full Range) Unit of Measure: months
	NA ^[1] (4.0 to 77.4)

[1]

Median was not reached due to insufficient number of events, i.e., (too few participants had reached progression at data cutoff.)

4.Secondary Outcome


Title	Overall Survival (OS)
Description	Survival curves for OS will be estimated using the Kaplan-Meier method...
Description	Survival curves for OS will be estimated using the Kaplan-Meier method.
Time Frame	Time interval between the start of treatment to death due to any cause, assessed up to 60 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description:	Patients receive pembrolizumab IV o...
Arm/Group Description:	Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity. * NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years. Laboratory Biomarker Analysis: Ancillary studies Pembrolizumab: Given IV
Overall Number of Participants Analyzed	50
Median (95% Confidence Interval) Unit of Measure: months
	47.2 (26 to 68.4)

5.Secondary Outcome


Title	Incidence of Adverse Events (AEs) Graded Using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Description	Safety will be assessed by quantifying the toxicities and grades exper...
Description	Safety will be assessed by quantifying the toxicities and grades experienced by subjects including serious AEs (SAEs) and events of clinical interest. Safety and tolerability will be assessed by clinical review of all relevant parameters including AEs, laboratory tests, vital signs, and electrocardiogram measurements. Assessed number of participants who experienced grade 3 to 5 adverse events.
Time Frame	Up to 90 days post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description:	Patients receive pembrolizumab IV o...
Arm/Group Description:	Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity. * NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years. Laboratory Biomarker Analysis: Ancillary studies Pembrolizumab: Given IV
Overall Number of Participants Analyzed	50
Measure Type: Count of Participants Unit of Measure: Participants
Grade 3-5 Adverse Events	29 58.0%
Grade 3-5 Drug Related Adverse Events	15 30.0%

6.Other Pre-specified Outcome


Title	Immune Correlates of the Clinical Activity of Pembrolizumab
Description	This will include immunohistochemical and gene expression analysis foc...
Description	This will include immunohistochemical and gene expression analysis focusing on delineating the immune components and immunologic milieu within the tumor before therapy.
Time Frame	Baseline

Outcome Measure Data Not Reported

7.Other Pre-specified Outcome


Title	Merkel Polyomavirus (MCPyV)-Specific Immune Response, Assessed With Enzyme-linked Immunosorbent Spot and Serology Assays
Description	Responses will be assessed at baseline, after initiating therapy, and ...
Description	Responses will be assessed at baseline, after initiating therapy, and correlated with clinical responses over time. Among patients with corresponding MHC-peptide tetramers, pre- and post-treatment samples of circulating MCPyV-specific CD8 T cells will be isolated and subjected to deep immunophenotyping by messenger ribonucleic acid (mRNA) expression analysis.
Time Frame	After 2 years of treatment

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Serious Adverse Events and other (not including serious) adverse events were assessed for up to 36 months. All cause mortality was assessed for up to 60 months.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Treatment (Pembrolizumab)
Arm/Group Description	Patients receive pembrolizumab IV o...
Arm/Group Description	Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 months in the absence of disease progression* or unacceptable toxicity. * NOTE: Patients with confirmed disease progression may continue to receive treatment if they are otherwise clinically stable until there is an increase in tumor burden of 25% or more following initial confirmation of progression. Under exceptional circumstances, and with protocol P.I. and CITN P.I. approval, patients may receive treatment beyond 2 years. Laboratory Biomarker Analysis: Ancillary studies Pembrolizumab: Given IV
All-Cause Mortality
	Treatment (Pembrolizumab)
	Affected / at Risk (%)
Total	16/50 (32.00%)
Serious Adverse Events Serious Adverse Events
	Treatment (Pembrolizumab)
	Affected / at Risk (%)
Total	22/50 (44.00%)
Blood and lymphatic system disorders
Anemia ^†	1/50 (2.00%)
Cardiac disorders
Atrial fibrillation ^†	1/50 (2.00%)
Myocarditis ^†	1/50 (2.00%)
Pericardial effusion ^†	1/50 (2.00%)
Sinus bradycardia ^†	1/50 (2.00%)
Ventricular arrhythmia ^†	1/50 (2.00%)
Gastrointestinal disorders
Abdominal pain ^†	1/50 (2.00%)
Colitis ^†	1/50 (2.00%)
Dysphagia ^†	1/50 (2.00%)
Gastrooesophageal reflux disease ^†	1/50 (2.00%)
Small intestinal haemorrhage ^†	2/50 (4.00%)
Small intestinal obstruction ^†	1/50 (2.00%)
Upper gastrointestinal haemorrhage ^†	2/50 (4.00%)
General disorders
Chills ^†	1/50 (2.00%)
Disease progression ^†	8/50 (16.00%)
Fatigue ^†	2/50 (4.00%)
Malaise ^†	1/50 (2.00%)
Pyrexia ^†	2/50 (4.00%)
Infections and infestations
Lung infection ^†	1/50 (2.00%)
Mastitis ^†	1/50 (2.00%)
Sepsis ^†	1/50 (2.00%)
Sialoadenitis ^†	1/50 (2.00%)
Streptococcal bacteraemia ^†	1/50 (2.00%)
Tuberculosis ^†	1/50 (2.00%)
Urinary tract infection ^†	1/50 (2.00%)
Investigations
Alanine aminotransferase increased ^†	2/50 (4.00%)
Aspartate aminotransferase increased ^†	3/50 (6.00%)
Blood alkaline phosphatase increased ^†	1/50 (2.00%)
Blood bilirubin increased ^†	1/50 (2.00%)
Metabolism and nutrition disorders
Acidosis ^†	1/50 (2.00%)
Decreased appetite ^†	1/50 (2.00%)
Dehydration ^†	4/50 (8.00%)
Hypercalcaemia ^†	1/50 (2.00%)
Hyperglycaemia ^†	2/50 (4.00%)
Hypernatraemia ^†	1/50 (2.00%)
Hyperuricaemia ^†	1/50 (2.00%)
Musculoskeletal and connective tissue disorders
Muscular weakness ^†	1/50 (2.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain ^†	1/50 (2.00%)
Paraneoplastic syndrome ^†	1/50 (2.00%)
Tumour pain ^†	1/50 (2.00%)
Psychiatric disorders
Delirium ^†	1/50 (2.00%)
Renal and urinary disorders
Acute kidney injury ^†	1/50 (2.00%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea ^†	1/50 (2.00%)
Epistaxis ^†	1/50 (2.00%)
Hypoxia ^†	1/50 (2.00%)
Pleural effusion ^†	1/50 (2.00%)
Pneumonitis ^†	2/50 (4.00%)
Skin and subcutaneous tissue disorders
Lichenoid keratosis ^†	1/50 (2.00%)
Pain of skin ^†	1/50 (2.00%)
Rash maculo-papular ^†	2/50 (4.00%)
Vascular disorders
Embolism ^†	3/50 (6.00%)
Haematoma ^†	2/50 (4.00%)
Hypotension ^†	1/50 (2.00%)
† Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	1%
	Treatment (Pembrolizumab)
	Affected / at Risk (%)
Total	50/50 (100.00%)
Blood and lymphatic system disorders
Anaemia ^†	16/50 (32.00%)
Leukocytosis ^†	3/50 (6.00%)
Leukopenia ^†	2/50 (4.00%)
Lymph node pain ^†	1/50 (2.00%)
Lymphadenopathy ^†	1/50 (2.00%)
Lymphopenia ^†	1/50 (2.00%)
Microcytic anaemia ^†	1/50 (2.00%)
Monocytosis ^†	1/50 (2.00%)
Thrombocytopenia ^†	2/50 (4.00%)
Cardiac disorders
Acute myocardial infarction ^†	1/50 (2.00%)
Atrial fibrillation ^†	1/50 (2.00%)
Bundle branch block left ^†	1/50 (2.00%)
Cardiac failure acute ^†	1/50 (2.00%)
Palpitations ^†	1/50 (2.00%)
Sinus bradycardia ^†	1/50 (2.00%)
Sinus tachycardia ^†	1/50 (2.00%)
Tachycardia ^†	1/50 (2.00%)
Ventricular tachycardia ^†	1/50 (2.00%)
Ear and labyrinth disorders
Deafness ^†	1/50 (2.00%)
Hypoacusis ^†	2/50 (4.00%)
Paraesthesia ear ^†	1/50 (2.00%)
Endocrine disorders
Adrenal insufficiency ^†	1/50 (2.00%)
Adrenocorticotropic hormone deficiency ^†	1/50 (2.00%)
Autoimmune hypothyroidism ^†	2/50 (4.00%)
Hyperthyroidism ^†	1/50 (2.00%)
Hypothyroidism ^†	3/50 (6.00%)
Thyroiditis ^†	1/50 (2.00%)
Eye disorders
Asthenopia ^†	1/50 (2.00%)
Diplopia ^†	1/50 (2.00%)
Eyelid ptosis ^†	1/50 (2.00%)
Ophthalmoplegia ^†	1/50 (2.00%)
Vision blurred ^†	1/50 (2.00%)
Visual acuity reduced ^†	1/50 (2.00%)
Visual impairment ^†	2/50 (4.00%)
Vitreous floaters ^†	2/50 (4.00%)
Gastrointestinal disorders
Abdominal discomfort ^†	3/50 (6.00%)
Abdominal distension ^†	1/50 (2.00%)
Abdominal pain ^†	5/50 (10.00%)
Abdominal pain upper ^†	2/50 (4.00%)
Aphthous ulcer ^†	1/50 (2.00%)
Breath odour ^†	1/50 (2.00%)
Colitis ^†	1/50 (2.00%)
Constipation ^†	14/50 (28.00%)
Diarrhoea ^†	11/50 (22.00%)
Dry mouth ^†	2/50 (4.00%)
Dyspepsia ^†	1/50 (2.00%)
Dysphagia ^†	1/50 (2.00%)
Faeces discoloured ^†	1/50 (2.00%)
Gastrointestinal haemorrhage ^†	1/50 (2.00%)
Gastrointestinal pain ^†	1/50 (2.00%)
Gastrooesophageal reflux disease ^†	4/50 (8.00%)
Haemorrhoids ^†	1/50 (2.00%)
Intra-abdominal haematoma ^†	1/50 (2.00%)
Large intestine polyp ^†	1/50 (2.00%)
Lower gastrointestinal haemorrhage ^†	1/50 (2.00%)
Nausea ^†	10/50 (20.00%)
Oesophageal varices haemorrhage ^†	1/50 (2.00%)
Pancreatitis ^†	2/50 (4.00%)
Stomatitis ^†	1/50 (2.00%)
Vomiting ^†	5/50 (10.00%)
General disorders
Asthenia ^†	2/50 (4.00%)
Chest discomfort ^†	1/50 (2.00%)
Chest pain ^†	1/50 (2.00%)
Chills ^†	4/50 (8.00%)
Cyst ^†	1/50 (2.00%)
Face oedema ^†	1/50 (2.00%)
Fatigue ^†	28/50 (56.00%)
Feeling cold ^†	1/50 (2.00%)
Feeling hot ^†	2/50 (4.00%)
Gait disturbance ^†	1/50 (2.00%)
Malaise ^†	1/50 (2.00%)
Nodule ^†	1/50 (2.00%)
Oedema ^†	1/50 (2.00%)
Oedema peripheral ^†	4/50 (8.00%)
Pain ^†	1/50 (2.00%)
Peripheral swelling ^†	4/50 (8.00%)
Pyrexia ^†	7/50 (14.00%)
Swelling ^†	2/50 (4.00%)
Temperature intolerance ^†	2/50 (4.00%)
Hepatobiliary disorders
Autoimmune hepatitis ^†	1/50 (2.00%)
Cholecystitis ^†	1/50 (2.00%)
Hyperbilirubinaemia ^†	1/50 (2.00%)
Immune system disorders
Seasonal allergy ^†	1/50 (2.00%)
Infections and infestations
Abdominal hernia infection ^†	1/50 (2.00%)
Abscess limb ^†	1/50 (2.00%)
Breast cellulitis ^†	1/50 (2.00%)
Bronchitis ^†	1/50 (2.00%)
Cellulitis ^†	3/50 (6.00%)
Conjunctivitis ^†	1/50 (2.00%)
Diverticulitis ^†	1/50 (2.00%)
Eye infection ^†	1/50 (2.00%)
Fungal infection ^†	1/50 (2.00%)
Gastrointestinal infection ^†	1/50 (2.00%)
Genital herpes ^†	1/50 (2.00%)
Herpes virus infection ^†	1/50 (2.00%)
Herpes zoster ^†	4/50 (8.00%)
Lung infection ^†	1/50 (2.00%)
Nasopharyngitis ^†	3/50 (6.00%)
Oral candidiasis ^†	3/50 (6.00%)
Oral herpes ^†	1/50 (2.00%)
Sinusitis ^†	3/50 (6.00%)
Skin infection ^†	1/50 (2.00%)
Soft tissue infection ^†	1/50 (2.00%)
Streptococcal infection ^†	1/50 (2.00%)
Upper respiratory tract infection ^†	14/50 (28.00%)
Urinary tract infection ^†	6/50 (12.00%)
Vaginal infection ^†	1/50 (2.00%)
Injury, poisoning and procedural complications
Contusion ^†	3/50 (6.00%)
Excoriation ^†	1/50 (2.00%)
Fall ^†	3/50 (6.00%)
Infusion related reaction ^†	1/50 (2.00%)
Tooth fracture ^†	1/50 (2.00%)
Investigations
Alanine aminotransferase increased ^†	11/50 (22.00%)
Amylase increased ^†	1/50 (2.00%)
Aspartate aminotransferase increased ^†	8/50 (16.00%)
Blood alkaline phosphatase decreased ^†	1/50 (2.00%)
Blood alkaline phosphatase increased ^†	7/50 (14.00%)
Blood bilirubin increased ^†	4/50 (8.00%)
Blood creatine phosphokinase increased ^†	2/50 (4.00%)
Blood creatinine increased ^†	6/50 (12.00%)
Blood glucose increased ^†	1/50 (2.00%)
Blood lactate dehydrogenase increased ^†	1/50 (2.00%)
Blood magnesium increased ^†	1/50 (2.00%)
Blood pressure increased ^†	1/50 (2.00%)
Blood testosterone decreased ^†	1/50 (2.00%)
Blood thyroid stimulating hormone increased ^†	1/50 (2.00%)
Blood urea increased ^†	1/50 (2.00%)
Blood urine present ^†	1/50 (2.00%)
Lipase increased ^†	1/50 (2.00%)
Lymphocyte count decreased ^†	7/50 (14.00%)
Neutrophil count decreased ^†	1/50 (2.00%)
Neutrophil count increased ^†	1/50 (2.00%)
Platelet count decreased ^†	2/50 (4.00%)
Sputum normal ^†	1/50 (2.00%)
Thyroxine free increased ^†	2/50 (4.00%)
Weight decreased ^†	5/50 (10.00%)
White blood cell count decreased ^†	5/50 (10.00%)
Metabolism and nutrition disorders
Decreased appetite ^†	11/50 (22.00%)
Dehydration ^†	1/50 (2.00%)
Hypercalcaemia ^†	2/50 (4.00%)
Hyperchloraemia ^†	2/50 (4.00%)
Hyperglycaemia ^†	11/50 (22.00%)
Hyperkalaemia ^†	4/50 (8.00%)
Hypernatraemia ^†	1/50 (2.00%)
Hyperuricaemia ^†	1/50 (2.00%)
Hypoalbuminaemia ^†	4/50 (8.00%)
Hypocalcaemia ^†	7/50 (14.00%)
Hypochloraemia ^†	2/50 (4.00%)
Hypokalaemia ^†	5/50 (10.00%)
Hypomagnesaemia ^†	1/50 (2.00%)
Hyponatraemia ^†	10/50 (20.00%)
Hypophosphataemia ^†	2/50 (4.00%)
Hypoproteinaemia ^†	2/50 (4.00%)
Hypovitaminosis ^†	1/50 (2.00%)
Increased appetite ^†	1/50 (2.00%)
Malnutrition ^†	1/50 (2.00%)
Musculoskeletal and connective tissue disorders
Arthralgia ^†	7/50 (14.00%)
Back pain ^†	4/50 (8.00%)
Bone pain ^†	1/50 (2.00%)
Flank pain ^†	1/50 (2.00%)
Groin pain ^†	1/50 (2.00%)
Joint range of motion decreased ^†	1/50 (2.00%)
Muscle fatigue ^†	1/50 (2.00%)
Muscle twitching ^†	1/50 (2.00%)
Muscular weakness ^†	5/50 (10.00%)
Musculoskeletal discomfort ^†	1/50 (2.00%)
Musculoskeletal pain ^†	3/50 (6.00%)
Myalgia ^†	6/50 (12.00%)
Neck mass ^†	1/50 (2.00%)
Osteoarthritis ^†	2/50 (4.00%)
Pain in extremity ^†	3/50 (6.00%)
Polyarthritis ^†	1/50 (2.00%)
Rotator cuff syndrome ^†	1/50 (2.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma ^†	1/50 (2.00%)
Lipoma ^†	1/50 (2.00%)
Melanocytic naevus ^†	1/50 (2.00%)
Paraneoplastic syndrome ^†	1/50 (2.00%)
Squamous cell carcinoma ^†	3/50 (6.00%)
Transitional cell carcinoma ^†	1/50 (2.00%)
Tumour pain ^†	2/50 (4.00%)
Nervous system disorders
Burning sensation ^†	2/50 (4.00%)
Cerebral ischaemia ^†	1/50 (2.00%)
Dizziness ^†	8/50 (16.00%)
Dysgeusia ^†	4/50 (8.00%)
Encephalopathy ^†	1/50 (2.00%)
Headache ^†	10/50 (20.00%)
Hyperaesthesia ^†	2/50 (4.00%)
Hypoaesthesia ^†	3/50 (6.00%)
Lethargy ^†	2/50 (4.00%)
Memory impairment ^†	1/50 (2.00%)
Nystagmus ^†	1/50 (2.00%)
Paraesthesia ^†	3/50 (6.00%)
Peripheral motor neuropathy ^†	1/50 (2.00%)
Peripheral sensory neuropathy ^†	1/50 (2.00%)
Sciatica ^†	3/50 (6.00%)
Syncope ^†	1/50 (2.00%)
Tremor ^†	2/50 (4.00%)
Psychiatric disorders
Anxiety ^†	1/50 (2.00%)
Confusional state ^†	1/50 (2.00%)
Delirium ^†	1/50 (2.00%)
Disorientation ^†	1/50 (2.00%)
Insomnia ^†	2/50 (4.00%)
Irritability ^†	2/50 (4.00%)
Mental status changes ^†	2/50 (4.00%)
Mood altered ^†	1/50 (2.00%)
Sleep disorder ^†	4/50 (8.00%)
Renal and urinary disorders
Acute kidney injury ^†	1/50 (2.00%)
Dysuria ^†	2/50 (4.00%)
Glycosuria ^†	2/50 (4.00%)
Haematuria ^†	3/50 (6.00%)
Nephritis ^†	1/50 (2.00%)
Nephrolithiasis ^†	1/50 (2.00%)
Pollakiuria ^†	1/50 (2.00%)
Proteinuria ^†	1/50 (2.00%)
Urinary retention ^†	1/50 (2.00%)
Urinary tract pain ^†	1/50 (2.00%)
Reproductive system and breast disorders
Breast pain ^†	3/50 (6.00%)
Breast swelling ^†	2/50 (4.00%)
Oedema genital ^†	1/50 (2.00%)
Pruritus genital ^†	1/50 (2.00%)
Respiratory, thoracic and mediastinal disorders
Cough ^†	11/50 (22.00%)
Dysphonia ^†	4/50 (8.00%)
Dyspnoea ^†	8/50 (16.00%)
Haemoptysis ^†	1/50 (2.00%)
Hypercapnia ^†	1/50 (2.00%)
Nasal congestion ^†	8/50 (16.00%)
Nasal polyps ^†	1/50 (2.00%)
Oropharyngeal pain ^†	3/50 (6.00%)
Pneumonitis ^†	1/50 (2.00%)
Productive cough ^†	1/50 (2.00%)
Respiratory tract congestion ^†	1/50 (2.00%)
Rhinorrhoea ^†	1/50 (2.00%)
Sinus congestion ^†	1/50 (2.00%)
Skin and subcutaneous tissue disorders
Actinic keratosis ^†	3/50 (6.00%)
Alopecia ^†	1/50 (2.00%)
Dry skin ^†	2/50 (4.00%)
Eczema ^†	2/50 (4.00%)
Erythema ^†	1/50 (2.00%)
Hair growth abnormal ^†	1/50 (2.00%)
Hypotrichosis ^†	1/50 (2.00%)
Itching scar ^†	1/50 (2.00%)
Lichen planus ^†	1/50 (2.00%)
Lichenoid keratosis ^†	2/50 (4.00%)
Night sweats ^†	2/50 (4.00%)
Papule ^†	1/50 (2.00%)
Pruritus ^†	11/50 (22.00%)
Pruritus generalised ^†	1/50 (2.00%)
Psoriasis ^†	1/50 (2.00%)
Rash ^†	11/50 (22.00%)
Rash erythematous ^†	2/50 (4.00%)
Rash maculo-papular ^†	7/50 (14.00%)
Rash pruritic ^†	2/50 (4.00%)
Skin burning sensation ^†	1/50 (2.00%)
Skin hyperpigmentation ^†	1/50 (2.00%)
Skin lesion ^†	1/50 (2.00%)
Surgical and medical procedures
Cancer surgery ^†	1/50 (2.00%)
Cataract operation ^†	1/50 (2.00%)
Vascular disorders
Deep vein thrombosis ^†	1/50 (2.00%)
Embolism ^†	1/50 (2.00%)
Haematoma ^†	2/50 (4.00%)
Hot flush ^†	5/50 (10.00%)
Hypertension ^†	6/50 (12.00%)
Hypotension ^†	4/50 (8.00%)
Lymphoedema ^†	1/50 (2.00%)
Phlebitis ^†	1/50 (2.00%)
† Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Administrative Director
Organization:	Cancer Immunotherapy Trials Network
Phone:	206-667-6609
EMail:	citn.core.reg@hvtn.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker A, Burgess MA, Hanks BA, Olencki T, Kendra K, Church C, Akaike T, Ramchurren N, Shinohara MM, Salim B, Taube JM, Jensen E, Kalabis M, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL. Three-year survival, correlates and salvage therapies in patients receiving first-line pembrolizumab for advanced Merkel cell carcinoma. J Immunother Cancer. 2021 Apr;9(4):e002478. doi: 10.1136/jitc-2021-002478.

Nghiem P, Bhatia S, Lipson EJ, Sharfman WH, Kudchadkar RR, Brohl AS, Friedlander PA, Daud A, Kluger HM, Reddy SA, Boulmay BC, Riker AI, Burgess MA, Hanks BA, Olencki T, Margolin K, Lundgren LM, Soni A, Ramchurren N, Church C, Park SY, Shinohara MM, Salim B, Taube JM, Bird SR, Ibrahim N, Fling SP, Homet Moreno B, Sharon E, Cheever MA, Topalian SL. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol. 2019 Mar 20;37(9):693-702. doi: 10.1200/JCO.18.01896. Epub 2019 Feb 6.

Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL, Cheever MA. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. N Engl J Med. 2016 Jun 30;374(26):2542-52. doi: 10.1056/NEJMoa1603702. Epub 2016 Apr 19.

Layout table for additonal information

Responsible Party:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT02267603
Other Study ID Numbers:	NCI-2014-00848 NCI-2014-00848 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) MK-3475 CITN-09 CITN-09 ( Other Identifier: Cancer Immunotherapy Trials Network ) CITN-09 ( Other Identifier: CTEP ) K24CA139052 ( U.S. NIH Grant/Contract ) P30CA015704 ( U.S. NIH Grant/Contract ) U01CA154967 ( U.S. NIH Grant/Contract )
First Submitted:	October 14, 2014
First Posted:	October 17, 2014
Results First Submitted:	February 5, 2019
Results First Posted:	March 1, 2019
Last Update Posted:	July 5, 2023

To Top