Study of Nivolumab in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) That Have Either Failed or Are Not Eligible for Autologous Stem Cell Transplant (CheckMate 139)

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02038933
• Collaborator: (none)
• Enrollment: 121
• Locations: 46
• Arm: 1
• Actual Duration (Months): 79.1
• Patients Per Site: 2.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether Nivolumab is effective in the treatment of DLBCL in patients that have failed or are ineligible for ASCT

Condition or Disease	Intervention/Treatment	Phase
Lymphoma. Non-Hodgkin	Drug: Nivolumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 121 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-Arm, Open-Label, Phase 2 Study of Nivolumab (BMS-936558) in Subjects With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) After Failure of Autologous Stem Cell Transplant (ASCT) or After Failure of At Least Two Prior Multi-Agent Chemotherapy Regimens in Subjects Who Are Not Candidates for ASCT
• Actual Study Start Date: Mar 5, 2014
• Actual Primary Completion Date: Apr 8, 2016
• Actual Study Completion Date: Oct 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab (3 mg/kg) Nivolumab 3 mg/kg solution intravenously every 2 weeks until progression or unacceptable toxicity	Drug: Nivolumab; Other Names: BMS-936558

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) Per Independent Radiologic Review Committee (IRRC) Assessment [From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assesed up to April 2016, approximately 25 months)]

   ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Remission (CR) or Partial Remission (PR), according to the 2007 revised International Working Group (IWG) Criteria for Malignant Lymphoma, , based on IRRC assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites

Secondary Outcome Measures

1. Duration of Response (DOR) [From date of first response to the date of documented disease progression or death, whichever occurs first (up to approximately 18 months)]

   DOR is defined as the time from first response (Complete Response (CR) or Partial Response (PR)) to the date of initial objectively documented progression as determined using the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites.

2. Complete Remission Rate [From date of first dose to study completion (up to approximately 78 months)]

   Complete Remission Rate is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan.

3. Duration of Complete Remission [From time of first documentation of CR to the date of initial documented disease progression or death due to any cause, whichever occurs first (up approximately 14 months)]

   The duration of Complete Remission is defined as the time from first documentation of Complete Response (CR) (which is the date of first negative FDG-PET scan or the date of first documentation of no disease involvement in the bone marrow [if required], whichever occurs later) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan.

4. Partial Remission Rate [From date of first dose to study completion (up to approximately 78 months)]

   Partial Remission rate is defined as the percentage of participants with a Best Overall Response (BOR) of Partial Response (PR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. PR= Regression of measurable disease and no emergence of new sites.

5. Duration of Partial Remission [From date of first documentation of PR to date of disease progression or death due to any cause, whichever occurs first (up to approximately 12 months)]

   Duration of Partial Remission is defined as the time from first documentation of Partial Response (PR) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. PR= Regression of measurable disease and no emergence of new sites.

6. Progression Free Survival [From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (up to approximately 2 months)]

   Progression Free Survival (PFS) is defined as the time from first dosing date to the date of the first documented progression, as determined by an Independent Radiology Review Committee (IRRC) according to the 2007 revised IWG Criteria for Malignant Lymphoma, or death due to any cause, whichever occurs first.

7. Objective Response Rate (ORR) Per Investigator Assessment [From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (up to approximately 30 months)]

   ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), according to investigator assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites.

Eligibility Criteria

Criteria

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

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Confirmation of relapsed or refractory DLBCL or transformed lymphoma (TL)

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 -1

• At least one lesion that measures >1.5 cm

• Prior therapy and screening lab criteria must be met

• Appropriate contraceptive measures must be taken

Exclusion Criteria:

• Known central nervous system (CNS) lymphoma

• History of interstitial lung disease, prior malignancy, active autoimmune disease, positive test for hepatitis B or hepatitis C virus

• Prior allogeneic stem cell transplant (SCT), chest radiation ≤ 24 weeks from study drug, ≥1000 mg of Carmustine Bis-chloroethylnitrosourea (BCNU) as part of pre-transplant conditioning regimen, prior treatment with drug targeting T-cell costimulation or immune checkpoint pathways

• Women who are breastfeeding or pregnant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic Arizona	Phoenix	Arizona	United States	85054
2	Division Of Hematology & Oncology Ctr. For Health Sciences	Los Angeles	California	United States	90095
3	Winship Cancer Center	Atlanta	Georgia	United States	30322
4	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
7	Columbia University Medical Center (Cumc)	New York	New York	United States	10019
8	Weill Cornell Medical College	New York	New York	United States	10021
9	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
10	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
11	Local Institution	Waratah	New South Wales	Australia	NSW 2298
12	Local Institution	Woodville	South Australia	Australia	5011
13	Local Institution	Heidelberg	Victoria	Australia	3084
14	Local Institution	B-leuven		Belgium	3000
15	Local Institution	Bruxelles		Belgium	1200
16	Local Institution	Gent		Belgium	9000
17	Local Institution	Montreal	Quebec	Canada	H3T 1E2
18	Local Institution	Montreal		Canada	H2X 3E4
19	Local Institution	Creteil		France	94010
20	Hopital Saint Eloi	Montpellier Cedex 05		France	34295
21	Local Institution	Pierre Benite Cedex		France	69495
22	Local Institution	Rennes		France	35033
23	Local Institution	Erlangen		Germany	91054
24	Local Institution	Essen		Germany	45147
25	Local Institution	Homburg		Germany	66424
26	Local Institution	Ulm		Germany	89081
27	Local Institution	Bergamo		Italy	24127
28	Local Institution	Bologna		Italy	40138
29	Local Institution	Milano		Italy	20133
30	Local Institution	Napoli		Italy	80131
31	Local Institution	Roma		Italy	00161
32	Local Institution	Amsterdam		Netherlands	1066 CX
33	Local Institution	Rotterdam		Netherlands	3000 CA
34	Local Institution	Rotterdam		Netherlands	3075 EA
35	Local Institution	Utrecht		Netherlands	3584 CX
36	Local Institution	Singapore		Singapore	119228
37	Local Institution	Singapore		Singapore	169608
38	Local Institution	Hospitalet Llobregat- Barcelona		Spain	9908
39	Local Institution	Madrid		Spain	28009
40	Hospital Universitario La Paz	Madrid		Spain	28046
41	Local Institution	Salamanca		Spain	37007
42	Local Institution	Gothenburg		Sweden	413 45
43	Local Institution	Lund		Sweden	221 85
44	Local Institution	Southampton	Hampshire	United Kingdom	SO16 6YD
45	Local Institution	Withington	Manchester	United Kingdom	M20 4BX
46	Local Institution	Sutton	Surrey	United Kingdom	SM2 5PT

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - Jul 21, 2016
• Statistical Analysis Plan - Oct 20, 2017

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02038933
• Other Study ID Numbers: CA209-139; 2013-003621-28
• First Posted: Jan 17, 2014
• Last Update Posted: Oct 14, 2021
• Last Verified: Oct 1, 2021

• Additional relevant MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse; Nivolumab

Study Results

Participant Flow

Pre-assignment Detail	121 participants entered the treatment period.

Arm/Group Title	Nivolumab 3mg/kg
Arm/Group Description	Nivolumab 3mg/kg IV Q2W for participants who failed autologous stem cell transplant (ASCT) or who were ineligible for ASCT
Period Title: Overall Study
STARTED	121
COMPLETED	0
NOT COMPLETED	121

Baseline Characteristics

Arm/Group Title	ASCT-failed	ASCT-ineligible	Total
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Total of all reporting groups
Overall Participants	87	34	121
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.1 (10.94)	66.4 (12.98)	61.1 (11.96)
Sex: Female, Male (Count of Participants)
Female	31 35.6%	13 38.2%	44 36.4%
Male	56 64.4%	21 61.8%	77 63.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2.3%	1 2.9%	3 2.5%
Not Hispanic or Latino	44 50.6%	20 58.8%	64 52.9%
Unknown or Not Reported	41 47.1%	13 38.2%	54 44.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	11 12.6%	1 2.9%	12 9.9%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 3.4%	2 5.9%	5 4.1%
White	71 81.6%	31 91.2%	102 84.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	2 2.3%	0 0%	2 1.7%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) Per Independent Radiologic Review Committee (IRRC) Assessment
Description	ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Remission (CR) or Partial Remission (PR), according to the 2007 revised International Working Group (IWG) Criteria for Malignant Lymphoma, , based on IRRC assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites
Time Frame	From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (assesed up to April 2016, approximately 25 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	ASCT-failed	ASCT-ineligible
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W
Measure Participants	87	34
Number (95% Confidence Interval) [Percent of participants]	10.3 11.8%	2.9 8.5%

2. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR is defined as the time from first response (Complete Response (CR) or Partial Response (PR)) to the date of initial objectively documented progression as determined using the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites.
Time Frame	From date of first response to the date of documented disease progression or death, whichever occurs first (up to approximately 18 months)

Outcome Measure Data

Analysis Population Description

All participants with CR or PR

Arm/Group Title	ASCT-failed	ASCT-ineligible
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W
Measure Participants	9	1
Median (95% Confidence Interval) [Months]	11.43	8.34

3. Secondary Outcome

Title	Complete Remission Rate
Description	Complete Remission Rate is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan.
Time Frame	From date of first dose to study completion (up to approximately 78 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	ASCT-failed	ASCT-ineligible
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W
Measure Participants	87	34
Number (95% Confidence Interval) [Percent of participants]	3.4 3.9%	0 0%

4. Secondary Outcome

Title	Duration of Complete Remission
Description	The duration of Complete Remission is defined as the time from first documentation of Complete Response (CR) (which is the date of first negative FDG-PET scan or the date of first documentation of no disease involvement in the bone marrow [if required], whichever occurs later) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. CR= Disappearance of all evidence of disease, confirmed by PET scan.
Time Frame	From time of first documentation of CR to the date of initial documented disease progression or death due to any cause, whichever occurs first (up approximately 14 months)

Outcome Measure Data

Analysis Population Description

All participants with CR

Arm/Group Title	ASCT-failed	ASCT-ineligible
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W
Measure Participants	3	0
Median (95% Confidence Interval) [Months]	NA

5. Secondary Outcome

Title	Partial Remission Rate
Description	Partial Remission rate is defined as the percentage of participants with a Best Overall Response (BOR) of Partial Response (PR) according to the 2007 revised IWG Criteria for Malignant Lymphoma, based on Independent Radiology Review Committee (IRRC) assessment. PR= Regression of measurable disease and no emergence of new sites.
Time Frame	From date of first dose to study completion (up to approximately 78 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	ASCT-failed	ASCT-ineligible
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W
Measure Participants	87	34
Number (95% Confidence Interval) [Percent of participants]	6.9 7.9%	2.9 8.5%

6. Secondary Outcome

Title	Duration of Partial Remission
Description	Duration of Partial Remission is defined as the time from first documentation of Partial Response (PR) to the date of initial objectively documented progression as determined using the 2007 IWG criteria, based on Independent Radiology Review Committee (IRRC) assessment, or death due to any cause, whichever occurs first. PR= Regression of measurable disease and no emergence of new sites.
Time Frame	From date of first documentation of PR to date of disease progression or death due to any cause, whichever occurs first (up to approximately 12 months)

Outcome Measure Data

Analysis Population Description

All participants with PR

Arm/Group Title	ASCT-failed	ASCT-ineligible
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W
Measure Participants	6	1
Median (Full Range) [Months]	6.64	8.34

7. Secondary Outcome

Title	Progression Free Survival
Description	Progression Free Survival (PFS) is defined as the time from first dosing date to the date of the first documented progression, as determined by an Independent Radiology Review Committee (IRRC) according to the 2007 revised IWG Criteria for Malignant Lymphoma, or death due to any cause, whichever occurs first.
Time Frame	From date of first dose to date of documented disease progression or death due to any cause, whichever occurs first (up to approximately 2 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	ASCT-failed	ASCT-ineligible
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W
Measure Participants	87	34
Median (95% Confidence Interval) [Months]	1.87	1.41

8. Secondary Outcome

Title	Objective Response Rate (ORR) Per Investigator Assessment
Description	ORR is defined as the percentage of participants with a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR), according to investigator assessment. CR= Disappearance of all evidence of disease, confirmed by PET scan; PR= Regression of measurable disease and no emergence of new sites.
Time Frame	From first dose until date of documented disease progression or subsequent therapy, whichever occurs first (up to approximately 30 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	ASCT-failed	ASCT-ineligible
Arm/Group Description	Participants who failed Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W	Participants who were ineligible for Autologous stem cell transplant (ASCT), treated with Nivolumab 3 mg/Kg Q2W
Measure Participants	87	34
Number (95% Confidence Interval) [Percent of participants]	19.5 22.4%	2.9 8.5%

Adverse Events

Time Frame	All-cause mortality was assessed from date of first dose to study completion (up to approximately 79 months). Serious Adverse events and other adverse events were assessed from date of first dose to 100 days following date of last dose (up to approximately 66 months)
Arm/Group Title	NIVOLUMAB 3 mg/kg
Arm/Group Description
All Cause Mortality
	NIVOLUMAB 3 mg/kg
	Affected / at Risk (%)	# Events
Total	98/121 (81%)
Serious Adverse Events
	NIVOLUMAB 3 mg/kg
	Affected / at Risk (%)	# Events
Total	83/121 (68.6%)
Blood and lymphatic system disorders
Abdominal lymphadenopathy	1/121 (0.8%)
Anaemia	2/121 (1.7%)
Febrile neutropenia	3/121 (2.5%)
Neutropenia	2/121 (1.7%)
Pancytopenia	1/121 (0.8%)
Thrombocytopenia	1/121 (0.8%)
Cardiac disorders
Arteriosclerosis coronary artery	1/121 (0.8%)
Atrial fibrillation	1/121 (0.8%)
Myocardial infarction	1/121 (0.8%)
Eye disorders
Eye swelling	1/121 (0.8%)
Uveitis	1/121 (0.8%)
Gastrointestinal disorders
Abdominal pain	5/121 (4.1%)
Ascites	1/121 (0.8%)
Diarrhoea	3/121 (2.5%)
Dysphagia	2/121 (1.7%)
Gastrointestinal perforation	1/121 (0.8%)
Intestinal obstruction	1/121 (0.8%)
Melaena	1/121 (0.8%)
Oesophageal perforation	1/121 (0.8%)
Pancreatitis	2/121 (1.7%)
Vomiting	2/121 (1.7%)
General disorders
Asthenia	1/121 (0.8%)
Facial pain	1/121 (0.8%)
General physical health deterioration	3/121 (2.5%)
Localised oedema	1/121 (0.8%)
Multiple organ dysfunction syndrome	1/121 (0.8%)
Oedema peripheral	1/121 (0.8%)
Pyrexia	4/121 (3.3%)
Swelling face	1/121 (0.8%)
Hepatobiliary disorders
Hyperbilirubinaemia	1/121 (0.8%)
Infections and infestations
Cellulitis	1/121 (0.8%)
Febrile infection	1/121 (0.8%)
Herpes zoster	1/121 (0.8%)
Kidney infection	2/121 (1.7%)
Neutropenic sepsis	1/121 (0.8%)
Peritonitis	1/121 (0.8%)
Pneumonia	7/121 (5.8%)
Pneumonia bacterial	1/121 (0.8%)
Sepsis	2/121 (1.7%)
Septic shock	1/121 (0.8%)
Sinusitis	1/121 (0.8%)
Tonsillitis	1/121 (0.8%)
Urinary tract infection	1/121 (0.8%)
Injury, poisoning and procedural complications
Tibia fracture	1/121 (0.8%)
Investigations
Transaminases increased	1/121 (0.8%)
Metabolism and nutrition disorders
Dehydration	1/121 (0.8%)
Failure to thrive	1/121 (0.8%)
Hypercalcaemia	6/121 (5%)
Hyperuricaemia	2/121 (1.7%)
Hyponatraemia	1/121 (0.8%)
Tumour lysis syndrome	2/121 (1.7%)
Musculoskeletal and connective tissue disorders
Back pain	1/121 (0.8%)
Bone lesion	1/121 (0.8%)
Morphoea	1/121 (0.8%)
Neck pain	1/121 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	1/121 (0.8%)
Diffuse large B-cell lymphoma	8/121 (6.6%)
Lung adenocarcinoma	1/121 (0.8%)
Malignant neoplasm progression	30/121 (24.8%)
Malignant pleural effusion	1/121 (0.8%)
Neoplasm malignant	2/121 (1.7%)
Neoplasm progression	1/121 (0.8%)
Nervous system disorders
Encephalopathy	1/121 (0.8%)
Headache	1/121 (0.8%)
IIIrd nerve paralysis	1/121 (0.8%)
Presyncope	1/121 (0.8%)
Transient ischaemic attack	1/121 (0.8%)
Psychiatric disorders
Confusional state	1/121 (0.8%)
Hallucination, visual	1/121 (0.8%)
Renal and urinary disorders
Acute kidney injury	5/121 (4.1%)
Renal impairment	1/121 (0.8%)
Urinary tract obstruction	1/121 (0.8%)
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	1/121 (0.8%)
Dyspnoea	2/121 (1.7%)
Hypoxia	2/121 (1.7%)
Lung disorder	1/121 (0.8%)
Obstructive airways disorder	1/121 (0.8%)
Pleural effusion	4/121 (3.3%)
Pneumonitis	1/121 (0.8%)
Respiratory failure	1/121 (0.8%)
Stridor	1/121 (0.8%)
Skin and subcutaneous tissue disorders
Rash	1/121 (0.8%)
Rash erythematous	1/121 (0.8%)
Rash maculo-papular	1/121 (0.8%)
Vascular disorders
Hypotension	2/121 (1.7%)
Other (Not Including Serious) Adverse Events
	NIVOLUMAB 3 mg/kg
	Affected / at Risk (%)	# Events
Total	109/121 (90.1%)
Blood and lymphatic system disorders
Anaemia	32/121 (26.4%)
Neutropenia	17/121 (14%)
Thrombocytopenia	20/121 (16.5%)
Gastrointestinal disorders
Abdominal pain	17/121 (14%)
Constipation	27/121 (22.3%)
Diarrhoea	25/121 (20.7%)
Dry mouth	7/121 (5.8%)
Nausea	41/121 (33.9%)
Stomatitis	7/121 (5.8%)
Vomiting	23/121 (19%)
General disorders
Asthenia	8/121 (6.6%)
Fatigue	49/121 (40.5%)
Oedema peripheral	17/121 (14%)
Pyrexia	29/121 (24%)
Infections and infestations
Nasopharyngitis	7/121 (5.8%)
Upper respiratory tract infection	9/121 (7.4%)
Investigations
Aspartate aminotransferase increased	8/121 (6.6%)
Blood creatinine increased	13/121 (10.7%)
Metabolism and nutrition disorders
Decreased appetite	23/121 (19%)
Hypercalcaemia	9/121 (7.4%)
Hyperglycaemia	9/121 (7.4%)
Hypokalaemia	10/121 (8.3%)
Hypomagnesaemia	8/121 (6.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/121 (15.7%)
Back pain	13/121 (10.7%)
Pain in extremity	13/121 (10.7%)
Nervous system disorders
Headache	14/121 (11.6%)
Psychiatric disorders
Anxiety	9/121 (7.4%)
Insomnia	11/121 (9.1%)
Respiratory, thoracic and mediastinal disorders
Cough	22/121 (18.2%)
Dyspnoea	19/121 (15.7%)
Skin and subcutaneous tissue disorders
Night sweats	8/121 (6.6%)
Pruritus	9/121 (7.4%)
Rash	16/121 (13.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.