Randomized Study of Nivolumab+Ipilimumab+/- SBRT for Metastatic Merkel Cell Carcinoma

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ClinicalTrials.gov Identifier: NCT03071406

Recruitment Status : Active, not recruiting

First Posted : March 6, 2017

Results First Posted : May 19, 2023

Last Update Posted : February 20, 2024

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Sponsor:

Collaborator:

Bristol-Myers Squibb

Information provided by (Responsible Party):

H. Lee Moffitt Cancer Center and Research Institute

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Conditions	Merkel Cell Carcinoma Skin Cancer
Interventions	Drug: Nivolumab Drug: Ipilimumab Radiation: Stereotactic Body Radiation Therapy (SBRT)
Enrollment	50

Participant Flow

Recruitment Details
Pre-assignment Details


Arm/Group Title	Arm A: Nivolumab + Ipilimumab	Arm B: Nivolumab + Ipilimumab + SBRT
Arm/Group Description	Nivolumab every 2 weeks and Ipilimu...	Nivolumab every 2 weeks and Ipilimu...
Arm/Group Description	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks. Stereotactic Body Radiation Therapy (SBRT): Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
Period Title: Overall Study
Started	25	25
Completed	25	24
Not Completed	0	1

Baseline Characteristics

Arm/Group Title		Arm A: Nivolumab + Ipilimumab	Arm B: Nivolumab + Ipilimumab + SBRT	Total
Arm/Group Description		Nivolumab every 2 weeks and Ipilimu...	Nivolumab every 2 weeks and Ipilimu...	Total of all reporting groups
Arm/Group Description		Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks. Stereotactic Body Radiation Therapy (SBRT): Stereotactic Body Radiation Therapy 24Gy in 3 fractions.	Total of all reporting groups
Overall Number of Baseline Participants		25	25	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	25 participants	25 participants	50 participants
	<=18 years	0 0.0%	0 0.0%	0 0.0%
	Between 18 and 65 years	6 24.0%	4 16.0%	10 20.0%
	>=65 years	19 76.0%	21 84.0%	40 80.0%
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	25 participants	25 participants	50 participants
	Female	5 20.0%	6 24.0%	11 22.0%
	Male	20 80.0%	19 76.0%	39 78.0%
Ethnicity (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	25 participants	25 participants	50 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	25 100.0%	25 100.0%	50 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB) Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	25 participants	25 participants	50 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	25 100.0%	25 100.0%	50 100.0%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment Measure Type: Number Unit of measure: Participants
United States	Number Analyzed	25 participants	25 participants	50 participants
United States		25	25	50

Outcome Measures

1.Primary Outcome


Title	Best Overall Response
Description	Overall response according to Immunotherapy Response Evaluation Criter...
Description	Overall response according to Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) including Complete Response (CR) + Partial Response (PR).
Time Frame	Up to 18 months

Outcome Measure Data

Analysis Population Description

Evaluable participants


Arm/Group Title	Arm A: Nivolumab + Ipilimumab	Arm B: Nivolumab + Ipilimumab + SBRT
Arm/Group Description:	Nivolumab every 2 weeks and Ipilimu...	Nivolumab every 2 weeks and Ipilimu...
Arm/Group Description:	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks. Stereotactic Body Radiation Therapy (SBRT): Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
Overall Number of Participants Analyzed	25	23
Measure Type: Count of Participants Unit of Measure: Participants
	18 72.0%	12 52.2%

2.Secondary Outcome


Title	Progression Free Survival (PFS)
Description	Median Progression Free Survival with 95% Confidence Interval. Progres...
Description	Median Progression Free Survival with 95% Confidence Interval. Progression is defined as progressive tumor lesions per immune-related Response Evaluation in Solid Tumors (irRECIST) definition, or appearance of one or more new Merkel cell carcinoma lesions, which can be local or distant in location from the irradiated lesions.
Time Frame	up to 28 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm A: Nivolumab + Ipilimumab	Arm B: Nivolumab + Ipilimumab + SBRT
Arm/Group Description:	Nivolumab every 2 weeks and Ipilimu...	Nivolumab every 2 weeks and Ipilimu...
Arm/Group Description:	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks. Stereotactic Body Radiation Therapy (SBRT): Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
Overall Number of Participants Analyzed	25	25
Median (95% Confidence Interval) Unit of Measure: months
	27.7 ^[1] (9.2 to NA)	7.6 ^[1] (2.8 to NA)

[1]

Not reached: the upper limit of the 95% confidence interval could not be calculated due to an insufficient number of participants with events

3.Secondary Outcome


Title	Overall Survival (OS)
Description	Median Overall Survival with 95% Confidence Interval. The length of ti...
Description	Median Overall Survival with 95% Confidence Interval. The length of time from the start of treatment until death from any cause.
Time Frame	Up to 30 months

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Arm A: Nivolumab + Ipilimumab	Arm B: Nivolumab + Ipilimumab + SBRT
Arm/Group Description:	Nivolumab every 2 weeks and Ipilimu...	Nivolumab every 2 weeks and Ipilimu...
Arm/Group Description:	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks. Stereotactic Body Radiation Therapy (SBRT): Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
Overall Number of Participants Analyzed	25	25
Median (95% Confidence Interval) Unit of Measure: months
	29.9 ^[1] (27.7 to NA)	16 ^[1] (11.3 to NA)

[1]

Not reached: the upper limit of the 95% confidence interval could not be calculated due to an insufficient number of participants with events

Adverse Events

Time Frame	Adverse events collected from on study date to 100 days after end of treatment (an average of 10.5 months). Survival will be assessed up to 5 years.
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Arm A: Nivolumab + Ipilimumab		Arm B: Nivolumab + Ipilimumab + SBRT
Arm/Group Description	Nivolumab every 2 weeks and Ipilimu...		Nivolumab every 2 weeks and Ipilimu...
Arm/Group Description	Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks.		Nivolumab every 2 weeks and Ipilimumab every 6 weeks until progression or unacceptable toxicity. Stereotactic Body Radiation Therapy (SBRT) to be given at the start of week 2. Nivolumab: Nivolumab 240 mg/dose intravenously (IV) every 2 (q2) weeks. Ipilimumab: Ipilimumab 1 mg/kg/dose IV q6 weeks. Stereotactic Body Radiation Therapy (SBRT): Stereotactic Body Radiation Therapy 24Gy in 3 fractions.
All-Cause Mortality
	Arm A: Nivolumab + Ipilimumab		Arm B: Nivolumab + Ipilimumab + SBRT
	Affected / at Risk (%)		Affected / at Risk (%)
Total	11/25 (44.00%)		15/25 (60.00%)
Serious Adverse Events Serious Adverse Events
	Arm A: Nivolumab + Ipilimumab		Arm B: Nivolumab + Ipilimumab + SBRT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/25 (52.00%)		13/25 (52.00%)
Blood and lymphatic system disorders
Anemia ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Febrile neutropenia ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Cardiac disorders
Myocarditis-autoimmune ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Atrial fibrilation ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Cardiac arrest ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Atrial Flutter ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Endocrine disorders
Adrenal insufficiency ^* 1	1/25 (4.00%)	2	0/25 (0.00%)	0
Gastrointestinal disorders
Abdominal pain ^* 1	0/25 (0.00%)	0	2/25 (8.00%)	3
Colitis ^* 1	1/25 (4.00%)	1	3/25 (12.00%)	5
Gastric ulcer ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Constipation ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Ascites ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Upper gastrointestinal hemorrhage ^* 1	1/25 (4.00%)	2	0/25 (0.00%)	0
Colonic hemorrhage ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Gallbladder obstruction ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Dysphagia ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	2
Nausea ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	2
Vomiting ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	2
Dehydration ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	2
Pancreatitis ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Diarrhea ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
General disorders
Pain ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Death NOS ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Non-cardiac chest pain ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Generalized weakness ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Hepatobiliary disorders
Biliary obstruction ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Infections and infestations
Lung infection ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Enterocolitis infection ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
MRSA ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	2
Urinary tract infection ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	2
Wound infection ^* 1	0/25 (0.00%)	0	2/25 (8.00%)	2
Infections and infestations - Other ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Injury, poisoning and procedural complications
Wound complication ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Injury, poisoning and procedural complications ^* 1 [1]	0/25 (0.00%)	0	1/25 (4.00%)	2
Fall ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Investigations
Alkaline phosphatase increased ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Lipase increased ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Metabolism and nutrition disorders
Tumor lysis syndrome ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Hyperglycemia ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Tumor pain ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Nervous system disorders
Syncope ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Psychiatric disorders
Insomnia ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	2
Renal and urinary disorders
Acute kidney injury ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Vocal fold paralysis ^* 1 [2]	0/25 (0.00%)	0	1/25 (4.00%)	2
Dyspnea ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Skin and subcutaneous tissue disorders
Skin Infection ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Rash maculo-papular ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Erythema multiforme ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
1 Term from vocabulary, CTCAE (4.0) * Indicates events were collected by non-systematic assessment [1] secretions due to recent tracheostomy [2] vocal fold paralysis exacerbated by clinical progression of tumor
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Arm A: Nivolumab + Ipilimumab		Arm B: Nivolumab + Ipilimumab + SBRT
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/25 (100.00%)		25/25 (100.00%)
Blood and lymphatic system disorders
Anemia ^* 1	6/25 (24.00%)	11	7/25 (28.00%)	13
Febrile neutropenia ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Cardiac disorders
Heart murmur ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Tachycardia ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Cardiac disorders - Other ^* 1 [1]	1/25 (4.00%)	1	0/25 (0.00%)	0
Atrial fibrillation ^* 1	3/25 (12.00%)	3	0/25 (0.00%)	0
Atrial flutter ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Cardiac arrest ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Myocarditis ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Palpitations ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Sinus brachycardia ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Sinus tachycardia ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Ear and labyrinth disorders
Hearing impaired ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Tinnitus ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Vertigo ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Ear and labyrinth disorders -Other ^* 1 [2]	1/25 (4.00%)	2	0/25 (0.00%)	0
Ear pain ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
External ear inflammation ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Endocrine disorders
Hypothyroidism ^* 1	5/25 (20.00%)	5	4/25 (16.00%)	4
Adrenal insufficiency ^* 1	5/25 (20.00%)	6	2/25 (8.00%)	2
Hyperthyroidism ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Endocrine disorders -Other ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Hyperparathyroidism ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Eye disorders
Blurred vision ^* 1	2/25 (8.00%)	3	3/25 (12.00%)	5
Dry eye ^* 1	2/25 (8.00%)	2	1/25 (4.00%)	1
Blepharitis ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Stye ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Eye disorders - Other ^* 1 [3]	1/25 (4.00%)	1	0/25 (0.00%)	0
Conjunctivitis ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Watering eyes ^* 1	0/25 (0.00%)	0	2/25 (8.00%)	2
Photophobia ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Gastrointestinal disorders
Diarrhea ^* 1	10/25 (40.00%)	21	13/25 (52.00%)	28
Nausea ^* 1	11/25 (44.00%)	17	10/25 (40.00%)	12
Constipation ^* 1	8/25 (32.00%)	15	5/25 (20.00%)	7
Abdominal pain ^* 1	4/25 (16.00%)	7	8/25 (32.00%)	12
Vomiting ^* 1	4/25 (16.00%)	4	7/25 (28.00%)	9
Colitis ^* 1	2/25 (8.00%)	2	8/25 (32.00%)	12
Dry mouth ^* 1	3/25 (12.00%)	4	3/25 (12.00%)	4
Dysphagia ^* 1	2/25 (8.00%)	2	3/25 (12.00%)	3
Gastroesophageal reflux disease ^* 1	0/25 (0.00%)	0	3/25 (12.00%)	3
Gastrointestinal disorders - Other ^* 1	2/25 (8.00%)	2	1/25 (4.00%)	1
Stomach pain ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Abdominal distension ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Ascites ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Bloating ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Colonic hemorrhage ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Dyspepsia ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Flatulence ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Gastric ulcer ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Hemorrhoids ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Mucositis oral ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Pancreatitis ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Upper gastrointestinal hemorrhage ^* 1	1/25 (4.00%)	2	0/25 (0.00%)	0
General disorders
Fatigue ^* 1	19/25 (76.00%)	37	15/25 (60.00%)	23
Edema limbs ^* 1	7/25 (28.00%)	9	9/25 (36.00%)	11
Pain ^* 1	6/25 (24.00%)	6	5/25 (20.00%)	8
General disorders and administration site conditions - Other ^* 1	4/25 (16.00%)	4	2/25 (8.00%)	4
Fever ^* 1	4/25 (16.00%)	4	1/25 (4.00%)	2
Flu like symptoms ^* 1	3/25 (12.00%)	4	2/25 (8.00%)	3
Infusion related reaction ^* 1	2/25 (8.00%)	3	1/25 (4.00%)	1
Chills ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Localized edema ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Non-cardiac chest pain ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Death NOS ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Edema face ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Gait disturbance ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Irritability ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Malaise ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Hepatobiliary disorders
Bile duct stenosis ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Biliary obstruction ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Immune system disorders
Autoimmune disorder ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Systemic inflammation syndrome ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Infections and infestations
Endocarditis ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Kidney infection ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
COVID-19 ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Infections and infestations - Other ^* 1 [4]	1/25 (4.00%)	1	0/25 (0.00%)	0
Infections and infestations - Other ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Urinary tract infection ^* 1	1/25 (4.00%)	2	3/25 (12.00%)	3
Wound infection ^* 1	1/25 (4.00%)	1	3/25 (12.00%)	4
Lung infection ^* 1	1/25 (4.00%)	1	2/25 (8.00%)	2
Rash pustular ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Sinusitis ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Upper respiratory infection ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Mucosal infection ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Skin infection ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Vaginal infection ^* 1	1/25 (4.00%)	2	0/25 (0.00%)	0
Injury, poisoning and procedural complications
Fall ^* 1	3/25 (12.00%)	5	2/25 (8.00%)	2
Bruising ^* 1	4/25 (16.00%)	5	0/25 (0.00%)	0
Injury, poisoning and procedural complications - Other ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Dermatitis radiation ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Fracture ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Seroma ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	2
Wound complication ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Investigations
Weight loss ^* 1	8/25 (32.00%)	12	6/25 (24.00%)	8
Lipase increased ^* 1	7/25 (28.00%)	15	4/25 (16.00%)	14
Serum amylase increased ^* 1	7/25 (28.00%)	19	4/25 (16.00%)	8
Aspartate aminotransferase increased ^* 1	7/25 (28.00%)	21	3/25 (12.00%)	3
Alanine aminotransferase increased ^* 1	6/25 (24.00%)	35	3/25 (12.00%)	4
Alkaline phosphatase increased ^* 1	3/25 (12.00%)	3	2/25 (8.00%)	2
Platelet count decreased ^* 1	2/25 (8.00%)	2	2/25 (8.00%)	2
Blood bilirubin increased ^* 1	1/25 (4.00%)	2	1/25 (4.00%)	1
Creatinine increased ^* 1	1/25 (4.00%)	8	1/25 (4.00%)	5
Weight gain ^* 1	1/25 (4.00%)	2	1/25 (4.00%)	1
White blood cell decreased ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
CPK increased ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Electrocardiogram QT corrected interval prolonged ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Lymphocyte count decreased ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Urine output decreased ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Metabolism and nutrition disorders
Anorexia ^* 1	5/25 (20.00%)	5	12/25 (48.00%)	14
Hyponatremia ^* 1	7/25 (28.00%)	12	5/25 (20.00%)	6
Hyperkalemia ^* 1	5/25 (20.00%)	9	4/25 (16.00%)	5
Dehydration ^* 1	2/25 (8.00%)	3	6/25 (24.00%)	6
Hyperglycemia ^* 1	6/25 (24.00%)	14	2/25 (8.00%)	3
Hypokalemia ^* 1	2/25 (8.00%)	4	4/25 (16.00%)	4
Hypercalcemia ^* 1	1/25 (4.00%)	1	4/25 (16.00%)	4
Hypoalbuminemia ^* 1	1/25 (4.00%)	1	2/25 (8.00%)	2
Hypomagnesemia ^* 1	2/25 (8.00%)	2	1/25 (4.00%)	2
Hypermagnesemia ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Hypocalcemia ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	2
Hypernatremia ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Hypertriglyceridemia ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Hypoglycemia ^* 1	1/25 (4.00%)	5	0/25 (0.00%)	0
Metabolism and nutrition disorders - Other ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Tumor lysis syndrome ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Musculoskeletal and connective tissue disorders
Arthralgia ^* 1	7/25 (28.00%)	14	7/25 (28.00%)	16
Myalgia ^* 1	5/25 (20.00%)	5	3/25 (12.00%)	3
Generalized muscle weakness ^* 1	3/25 (12.00%)	3	3/25 (12.00%)	4
Back pain ^* 1	3/25 (12.00%)	3	2/25 (8.00%)	2
Pain in extremity ^* 1	3/25 (12.00%)	4	2/25 (8.00%)	3
Arthritis ^* 1	2/25 (8.00%)	4	1/25 (4.00%)	1
Muscle weakness upper limb ^* 1	1/25 (4.00%)	1	2/25 (8.00%)	2
Musculoskeletal and connective tissue disorder - Other ^* 1	1/25 (4.00%)	1	2/25 (8.00%)	2
Neck pain ^* 1	0/25 (0.00%)	0	3/25 (12.00%)	3
Buttock pain ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Chest wall pain ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Flank pain ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Joint range of motion decreased ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Muscle weakness lower limb ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other ^* 1 [5]	8/25 (32.00%)	11	7/25 (28.00%)	8
Tumor pain ^* 1	2/25 (8.00%)	2	2/25 (8.00%)	2
Nervous system disorders
Headache ^* 1	6/25 (24.00%)	12	7/25 (28.00%)	8
Dizziness ^* 1	5/25 (20.00%)	6	6/25 (24.00%)	6
Dysgeusia ^* 1	4/25 (16.00%)	4	2/25 (8.00%)	2
Nervous system disorders - Other ^* 1	1/25 (4.00%)	1	2/25 (8.00%)	3
Memory impairment ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Parasthesia ^* 1	1/25 (4.00%)	2	1/25 (4.00%)	2
Syncope ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Concentration impairment ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Encephalopathy ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Peripheral motor neuropathy ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Peripheral sensory neuropathy ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Presyncope ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Sinus pain ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Transient ischemic attacks ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Tremor ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Vasovagal reaction ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Psychiatric disorders
Depression ^* 1	3/25 (12.00%)	3	3/25 (12.00%)	3
Insomnia ^* 1	2/25 (8.00%)	3	4/25 (16.00%)	4
Confusion ^* 1	2/25 (8.00%)	2	1/25 (4.00%)	1
Anxiety ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Renal and urinary disorders
Acute kidney injury ^* 1	2/25 (8.00%)	2	2/25 (8.00%)	5
Hematuria ^* 1	2/25 (8.00%)	3	2/25 (8.00%)	2
Renal calculi ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Chronic kidney disease ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Renal and urinary disorders - Other ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Renal colic ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Urinary frequency ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Urinary incontinence ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Urinary tract obstruction ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Urinary tract pain ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Urine discoloration ^* 1	1/25 (4.00%)	2	0/25 (0.00%)	0
Reproductive system and breast disorders
Perineal pain ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Testicular pain ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Cough ^* 1	8/25 (32.00%)	13	11/25 (44.00%)	14
Dyspnea ^* 1	5/25 (20.00%)	7	8/25 (32.00%)	11
Postnasal drip ^* 1	1/25 (4.00%)	1	5/25 (20.00%)	5
Allergic rhinitis ^* 1	3/25 (12.00%)	3	2/25 (8.00%)	2
Nasal congestion ^* 1	2/25 (8.00%)	3	3/25 (12.00%)	4
Sore throat ^* 1	1/25 (4.00%)	1	3/25 (12.00%)	3
Productive cough ^* 1	3/25 (12.00%)	3	0/25 (0.00%)	0
Epistaxis ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Pneumonitis ^* 1	2/25 (8.00%)	4	0/25 (0.00%)	0
Respiratory, thoracic and mediastinal disorders - Other ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	2
Hoarseness ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Hypoxia ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Pleural effusion ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Respiratory failure ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Stridor ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Voice alteration ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Skin and subcutaneous tissue disorders
Skin lesions ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Actinic Keratoses ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Itching rash ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Minor rash ^* 1	8/25 (32.00%)	10	0/25 (0.00%)	0
Macular rash ^* 1	2/25 (8.00%)	2	0/25 (0.00%)	0
Skin and subcutaneous tissues disorders - Other ^* 1 [6]	1/25 (4.00%)	2	0/25 (0.00%)	0
Skin and subcutaneous tissue disorders - Other ^* 1 [7]	1/25 (4.00%)	1	0/25 (0.00%)	0
Pruritus ^* 1	11/25 (44.00%)	18	10/25 (40.00%)	15
Rash maculo-papular ^* 1	3/25 (12.00%)	8	6/25 (24.00%)	14
Dry skin ^* 1	2/25 (8.00%)	2	4/25 (16.00%)	4
Erythema multiforme ^* 1	1/25 (4.00%)	1	1/25 (4.00%)	1
Skin ulceration ^* 1	0/25 (0.00%)	0	2/25 (8.00%)	2
Bullous dermatitis ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Photosensitivity ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Skin hypopigmentation ^* 1	1/25 (4.00%)	1	0/25 (0.00%)	0
Vascular disorders
Hypotension ^* 1	2/25 (8.00%)	2	4/25 (16.00%)	6
Hypertension ^* 1	2/25 (8.00%)	2	2/25 (8.00%)	3
Lymphedema ^* 1	1/25 (4.00%)	1	2/25 (8.00%)	2
Hematoma ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
Hot flashes ^* 1	0/25 (0.00%)	0	1/25 (4.00%)	1
1 Term from vocabulary, CTCAE (4.0) * Indicates events were collected by non-systematic assessment [1] Dilated ascending thoracic aorta measures 4.5 cm [2] Had a sensation and "sound" that there was fluid [3] Patient reports change in eyesight [4] Patient reported he has a cold, for which hisPCP treated him with prednisone and amoxicillin [5] skin lesion, scheduled for biopsy [6] left forearm lesion [7] Slight drainage from a couple of the larger lesions with occasional blood tinged discharge from leg lesions

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT 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

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Name/Title:	Sungjune Kim, MD, PhD
Organization:	Moffitt Cancer Center
Phone:	813-745-1898
EMail:	sungjune.kim@moffitt.org

Publications:

Kim S, Wuthrick E, Blakaj D, Eroglu Z, Verschraegen C, Thapa R, Mills M, Dibs K, Liveringhouse C, Russell J, Caudell JJ, Tarhini A, Markowitz J, Kendra K, Wu R, Chen DT, Berglund A, Michael L, Aoki M, Wang MH, Hamaidi I, Cheng P, de la Iglesia J, Slebos RJ, Chung CH, Knepper TC, Moran-Segura CM, Nguyen JV, Perez BA, Rose T, Harrison L, Messina JL, Sondak VK, Tsai KY, Khushalani NI, Brohl AS. Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial. Lancet. 2022 Sep 24;400(10357):1008-1019. doi: 10.1016/S0140-6736(22)01659-2. Epub 2022 Sep 12.

Layout table for additonal information

Responsible Party:	H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:	NCT03071406
Other Study ID Numbers:	MCC-18786 CA209-737 ( Other Identifier: Bristol-Myers Squibb )
First Submitted:	March 1, 2017
First Posted:	March 6, 2017
Results First Submitted:	April 3, 2023
Results First Posted:	May 19, 2023
Last Update Posted:	February 20, 2024

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