CheckMate 627: An Open Label Investigational Immuno-therapy Trial of Nivolumab in Cancers That Are Advanced or Have Spread

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02832167
• Collaborator: (none)
• Enrollment: 239
• Locations: 45
• Arm: 1
• Actual Duration (Months): 64
• Patients Per Site: 5.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether nivolumab is an effective treatment for cancer that has advanced or has spread. Various tumor types may be eligible for enrollment.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Biological: Nivolumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 239 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Phase 2 Multi-cohort Trial of Nivolumab in Advanced or Metastatic Malignancies
• Actual Study Start Date: Feb 22, 2016
• Actual Primary Completion Date: Oct 20, 2019
• Actual Study Completion Date: Jun 24, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nivolumab	Biological: Nivolumab; Specified dose on specified days; Other Names: BMS-936558 Opdivo

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) [From first dose to the date of objectively documented progression (per tumor-specific response criteria) or the date of subsequent therapy, whichever occurs first (up to approximately 24 months)]

   ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR). Best overall response is defined as the best response designation, as determined by investigator, recorded in the specified timeframe, according to the RECIST 1.1 criteria.

Secondary Outcome Measures

1. Duration of Response (DOR) [From the time of first confirmed response to the date of the first documented progression (up to approximately 22 months)]

   DOR is defined as the time from first confirmed response (Complete Response, CR or Partial Response, PR) to the date of the first documented tumor progression (as determined by investigator) or death due to any cause, whichever occurs first. Median DOR computed using Kaplan-Meier method

2. Time to Objective Response (TTR) [From the first dosing date to the date of the first confirmed response (up to approximately 10 months)]

   TTR is defined as the time from first dosing date to the date of the first confirmed response (Complete Response, CR or Partial Response, PR), as assessed by investigator.

3. Clinical Benefit Rate (CBR) [From the first dosing date to the date of the last dose (approximately 24 months)]

   CBR is defined as the percentage of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) or Stable Disease (SD).

4. Overall Survival Rate at 1 Year [From the first dosing date to 1 year later]

   Overall Survival (OS) is defined as the time from the first dosing date to the date of death. A participant who has not died will be censored at last known date alive. OS rate at 1 year is measured as the percent of participants still alive at 1 year after first dosing, measured from Kaplan-Meier curve of OS.

5. Number of Participants Who Died [From first dose to 100 days following last dose (up approximately 27 months)]

   Number of participants who died for any cause

6. Number of Participants Experiencing Adverse Events (AEs) [From first dose to 30 days following the last dose (up to approximately 25 months)]

   Number of participants who experienced any grade, any cause AEs

7. Number of Participants Experiencing Serious Adverse Events (SAEs) [From first dose to 100 days following the last dose (up to approximately 27 months)]

   Number of participants who experienced any grade, any cause SAEs

8. Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation [From first dose to 30 days following the last dose (up to approximately 25 months)]

   Number of participants who experienced AEs leading to discontinuation of study therapy

9. Number of Participants Experiencing Immune-mediated Adverse Events (IMAEs) [From first dose to 100 days following the last dose (up to approximately 27 months)]

   Number of participants who experienced IMAEs. IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.

10. Number of Participants Experiencing Select Adverse Events [From first dose to 30 days following the last dose (up to approximately 25 months)]

    Number of participants who experienced Select Adverse Events. Select Adverse Events categories include: gastrointestinal, hepatic, pulmonary, renal, skin, hypersensitivity/infusion reaction.

11. Number of Participants Experiencing Adverse Events (AEs) Leading to Dose Delay or Dose Reduction [From first dose to 30 days following the last dose (up to approximately 25 months)]

    Number of participants who experienced AEs leading to dose delay or dose reduction. A dose will be considered as delayed if the delay is exceeding 3 days after the intended dose date (i.e., greater than or equal to 4 days from scheduled dosing date)

12. Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests [From first dose to 30 days following the last dose (up to approximately 25 months)]

    Number of participants who experienced the laboratory abnormalities in specific liver tests described in the individual categories. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal

13. Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests [From first dose to 100 days following the last dose (up to approximately 27 months)]

    Number of participants who experienced the laboratory abnormalities in specific thyroid tests described in the individual categories. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Diagnosed with advanced or metastatic malignancy

• Received standard of care treatment for primary malignancy and standard of care treatment for relapsed cancer

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

Exclusion Criteria:

• Prior treatment with an antiPD1, antiPDL1, antiPDL2, antiCD137, or antiCTLA4 antibody, or any other antibody or drug specifically targeting Tcell co-stimulation or checkpoint pathways.

• Subjects previously treated with investigational anticancer therapies less than 6 weeks prior to the first dose of Nivolumab

• Subjects with an active, known, or suspected autoimmune disease

Other protocol-defined inclusion/exclusion criteria apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Oncology Associates, PC	Tucson	Arizona	United States	85711
2	CBCC Global Research, Inc. at Comprehensive Blood and Cancer Center	Bakersfield	California	United States	93309
3	St. Jude Hospital Yorba Linda	Fullerton	California	United States	92835
4	LACN	Los Angeles	California	United States	90017
5	UCLA Main Campus - University California Los Angeles	Los Angeles	California	United States	90095
6	Torrence Health Association, DBA Torrance Memorial;Physician Network/Cancer Care Associates	Redondo Beach	California	United States	90277
7	Coastal Integrative Cancer Care	San Luis Obispo	California	United States	93401
8	Cancer Center of Santa Barbara with Sansum Clinic	Santa Barbara	California	United States	93105
9	Central Coast Medical Oncology Corporation	Santa Maria	California	United States	93454
10	Rocky Mountain Cancer Centers - Denver Midtwon	Denver	Colorado	United States	80218
11	St. Mary's Hospital And Regional Medical Center	Grand Junction	Colorado	United States	81501
12	Memorial Healthcare System	Hollywood	Florida	United States	33021
13	Florida Cancer Affiliates	Ocala	Florida	United States	34471
14	Orlando Health, Inc	Orlando	Florida	United States	32806
15	Florida Cancer Specialists & Research Institute	Saint Petersburg	Florida	United States	33705
16	Florida Cancer Specialists	West Palm Beach	Florida	United States	33401
17	Illinois Cancer Specialists	Niles	Illinois	United States	60714
18	Fort Wayne Medical Oncology and Hematology, Inc.	Fort Wayne	Indiana	United States	46845
19	Maryland Oncology Hematology P.A.	Columbia	Maryland	United States	21044
20	Minnesota Oncology Hematology, P.A.	Minneapolis	Minnesota	United States	55404
21	HCA Midwest Healthcare	Kansas City	Missouri	United States	64132
22	Oncology Hematology West P.C. dba Nebraska Cancer Specialists	Omaha	Nebraska	United States	68130
23	Texas Oncology-Austin Central	Las Vegas	Nevada	United States	89148
24	Saint Barnabas Medical Cancer Center	Livingston	New Jersey	United States	07039
25	USOR - New York Oncology Hematology, P.C.	Albany	New York	United States	12206
26	Hematology Oncology Associates, PC	Medford	Oregon	United States	97504
27	Willamette Valley Cancer Institute and Research Center	Springfield	Oregon	United States	97477
28	Northwest Cancer Specialists, P.C.	Tualatin	Oregon	United States	97062
29	Greenville Health System	Greenville	South Carolina	United States	29615
30	West Cancer Center	Germantown	Tennessee	United States	38138
31	Tennessee Oncology	Lebanon	Tennessee	United States	37090
32	Texas Oncology - Baylor Charles A. Simmons Cancer Center	Dallas	Texas	United States	75246
33	Texas Oncology, P.A.	Fort Worth	Texas	United States	76104
34	The University of Texas MD Anderson Cancer Center-merge	Houston	Texas	United States	77030
35	Texas Oncology, P.A.	San Antonio	Texas	United States	78240
36	Texas Oncology The Woodlands	The Woodlands	Texas	United States	77380
37	Texas Oncology - Waco	Waco	Texas	United States	76712
38	Virginia Cancer Care Specialist, PC	Fairfax	Virginia	United States	22031
39	Oncology and Hematology Associates of Southwest Virginia, Inc., DBA Blue Ridge Cancer Care	Wytheville	Virginia	United States	24382
40	Local Institution	Berlin		Germany	12200
41	Local Institution	Bonn		Germany	53127
42	Local Institution	Dresden		Germany	01307
43	Local Institution	Essen		Germany	45147
44	Local Institution	Freiburg		Germany	79106
45	Klinikum Rechts der Isar der Technischen Universitaet Muenchen	Muenchen		Germany	81675

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

• Study Protocol - May 31, 2018
• Statistical Analysis Plan - Jun 24, 2018

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02832167
• Other Study ID Numbers: CA209-627; 2016-000461-23
• First Posted: Jul 14, 2016
• Last Update Posted: May 9, 2022
• Last Verified: Apr 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Nivolumab

Study Results

Participant Flow

Pre-assignment Detail	239 participants were treated.

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Period Title: Treatment Period 1
STARTED	239
COMPLETED	110
NOT COMPLETED	129
Period Title: Treatment Period 1
STARTED	110
COMPLETED	103
NOT COMPLETED	7
Period Title: Treatment Period 1
STARTED	103
COMPLETED	19
NOT COMPLETED	84

Baseline Characteristics

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Overall Participants	239
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.2 (13.79)
Sex: Female, Male (Count of Participants)
Female	148 61.9%
Male	91 38.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	11 4.6%
Not Hispanic or Latino	158 66.1%
Unknown or Not Reported	70 29.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	9 3.8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	20 8.4%
White	203 84.9%
More than one race	0 0%
Unknown or Not Reported	7 2.9%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR)
Description	ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR). Best overall response is defined as the best response designation, as determined by investigator, recorded in the specified timeframe, according to the RECIST 1.1 criteria.
Time Frame	From first dose to the date of objectively documented progression (per tumor-specific response criteria) or the date of subsequent therapy, whichever occurs first (up to approximately 24 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Number (95% Confidence Interval) [Percent of Participants]	7.9 3.3%

2. Secondary Outcome

Title	Duration of Response (DOR)
Description	DOR is defined as the time from first confirmed response (Complete Response, CR or Partial Response, PR) to the date of the first documented tumor progression (as determined by investigator) or death due to any cause, whichever occurs first. Median DOR computed using Kaplan-Meier method
Time Frame	From the time of first confirmed response to the date of the first documented progression (up to approximately 22 months)

Outcome Measure Data

Analysis Population Description

All Responders (Participants with a confirmed CR or PR)

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	19
Median (Full Range) [Months]	21.78

3. Secondary Outcome

Title	Time to Objective Response (TTR)
Description	TTR is defined as the time from first dosing date to the date of the first confirmed response (Complete Response, CR or Partial Response, PR), as assessed by investigator.
Time Frame	From the first dosing date to the date of the first confirmed response (up to approximately 10 months)

Outcome Measure Data

Analysis Population Description

All Responders (Participants with a confirmed CR or PR)

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	19
Mean (Standard Deviation) [Months]	3.54 (2.337)

4. Secondary Outcome

Title	Clinical Benefit Rate (CBR)
Description	CBR is defined as the percentage of participants with a best overall response of confirmed Complete Response (CR) or Partial Response (PR) or Stable Disease (SD).
Time Frame	From the first dosing date to the date of the last dose (approximately 24 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Number (95% Confidence Interval) [Percent of participants]	49.8 20.8%

5. Secondary Outcome

Title	Overall Survival Rate at 1 Year
Description	Overall Survival (OS) is defined as the time from the first dosing date to the date of death. A participant who has not died will be censored at last known date alive. OS rate at 1 year is measured as the percent of participants still alive at 1 year after first dosing, measured from Kaplan-Meier curve of OS.
Time Frame	From the first dosing date to 1 year later

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Number (95% Confidence Interval) [Percent of participants]	56.1 23.5%

6. Secondary Outcome

Title	Number of Participants Who Died
Description	Number of participants who died for any cause
Time Frame	From first dose to 100 days following last dose (up approximately 27 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Count of Participants [Participants]	72 30.1%

7. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events (AEs)
Description	Number of participants who experienced any grade, any cause AEs
Time Frame	From first dose to 30 days following the last dose (up to approximately 25 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Count of Participants [Participants]	234 97.9%

8. Secondary Outcome

Title	Number of Participants Experiencing Serious Adverse Events (SAEs)
Description	Number of participants who experienced any grade, any cause SAEs
Time Frame	From first dose to 100 days following the last dose (up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Count of Participants [Participants]	148 61.9%

9. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Description	Number of participants who experienced AEs leading to discontinuation of study therapy
Time Frame	From first dose to 30 days following the last dose (up to approximately 25 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Count of Participants [Participants]	41 17.2%

10. Secondary Outcome

Title	Number of Participants Experiencing Immune-mediated Adverse Events (IMAEs)
Description	Number of participants who experienced IMAEs. IMAEs are AEs consistent with an immune-mediated mechanism or immune-mediated component for which non-inflammatory etiologies (eg, infection or tumor progression) have been ruled out. IMAEs can include events with an alternate etiology which were exacerbated by the induction of autoimmunity.
Time Frame	From first dose to 100 days following the last dose (up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Count of Participants [Participants]	8 3.3%

11. Secondary Outcome

Title	Number of Participants Experiencing Select Adverse Events
Description	Number of participants who experienced Select Adverse Events. Select Adverse Events categories include: gastrointestinal, hepatic, pulmonary, renal, skin, hypersensitivity/infusion reaction.
Time Frame	From first dose to 30 days following the last dose (up to approximately 25 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Gastrointestinal Select AEs	57 23.8%
Hepatic Select AEs	33 13.8%
Pulmonary Select AEs	6 2.5%
Renal Select AEs	22 9.2%
Skin Select AEs	59 24.7%
Hypersensitivity/Infusion Reaction	7 2.9%

12. Secondary Outcome

Title	Number of Participants Experiencing Adverse Events (AEs) Leading to Dose Delay or Dose Reduction
Description	Number of participants who experienced AEs leading to dose delay or dose reduction. A dose will be considered as delayed if the delay is exceeding 3 days after the intended dose date (i.e., greater than or equal to 4 days from scheduled dosing date)
Time Frame	From first dose to 30 days following the last dose (up to approximately 25 months)

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	239
Count of Participants [Participants]	61 25.5%

13. Secondary Outcome

Title	Number of Participants Experiencing Laboratory Abnormalities in Specific Liver Tests
Description	Number of participants who experienced the laboratory abnormalities in specific liver tests described in the individual categories. ALT = Alanine Aminotransferase AST = Aspartate Aminotransferase ULN = Upper Limit of Normal
Time Frame	From first dose to 30 days following the last dose (up to approximately 25 months)

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	231
ALT OR AST > 3XULN	11 4.6%
ALT OR AST > 5XULN	8 3.3%
ALT OR AST > 10XULN	3 1.3%
ALT OR AST > 20XULN	1 0.4%
TOTAL BILIRUBIN > 2XULN	5 2.1%
ALT OR AST > 3XULN + BILIRUBIN > 2XULN WITHIN 1 DAY	3 1.3%
ALT OR AST > 3XULN + BILIRUBIN > 2XULN WITHIN 30 DAYS	3 1.3%

14. Secondary Outcome

Title	Number of Participants Experiencing Laboratory Abnormalities in Specific Thyroid Tests
Description	Number of participants who experienced the laboratory abnormalities in specific thyroid tests described in the individual categories. TSH = Thyroid Stimulating Hormone LLN = Lower Limit of Normal ULN = Upper Limit of Normal
Time Frame	From first dose to 100 days following the last dose (up to approximately 27 months)

Outcome Measure Data

Analysis Population Description

All treated participants with available measurements

Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
Measure Participants	238
TSH > ULN	62 25.9%
TSH > ULN WITH TSH <= ULN AT BASELINE	42 17.6%
TSH > ULN WITH AT LEAST ONE FT3/FT4 TEST VALUE < LLN	12 5%
TSH > ULN WITH ALL OTHER FT3/FT4 TEST VALUE >= LLN	0 0%
TSH > ULN WITH FT3/FT4 MISSING	2 0.8%
TSH < LLN	38 15.9%
TSH < LLN WITH TSH >= LLN AT BASELINE	25 10.5%
TSH < LLN WITH AT LEAST ONE FT3/FT4 TEST VALUE > ULN	8 3.3%
TSH < LLN WITH ALL OTHER FT3/FT4 TEST VALUES <= ULN	1 0.4%
TSH < LLN WITH FT3/FT4 TEST MISSING	1 0.4%

Adverse Events

Time Frame	All-cause mortality was assessed from first dose to study completion date (approximately 64 months). SAEs and Other AEs were assessed from first dose to 100 days following administration of the last dose (approximately 27 months).
Arm/Group Title	Advanced Malignancies Cohort
Arm/Group Description	Treatment period 1: Nivolumab 240 mg Q2W for 8 doses. Treatment period 2: Nivolumab 480 mg Q4W
All Cause Mortality
	Advanced Malignancies Cohort
	Affected / at Risk (%)	# Events
Total	156/239 (65.3%)
Serious Adverse Events
	Advanced Malignancies Cohort
	Affected / at Risk (%)	# Events
Total	148/239 (61.9%)
Blood and lymphatic system disorders
Anaemia	3/239 (1.3%)
Cardiac disorders
Acute myocardial infarction	1/239 (0.4%)
Cardiac arrest	1/239 (0.4%)
Cardiac failure congestive	1/239 (0.4%)
Cardio-respiratory arrest	1/239 (0.4%)
Myocardial infarction	2/239 (0.8%)
Supraventricular tachycardia	1/239 (0.4%)
Ventricular tachycardia	1/239 (0.4%)
Endocrine disorders
Hyperthyroidism	1/239 (0.4%)
Hypophysitis	1/239 (0.4%)
Eye disorders
Eye pain	1/239 (0.4%)
Eye swelling	1/239 (0.4%)
Gastrointestinal disorders
Abdominal pain	9/239 (3.8%)
Abdominal pain lower	1/239 (0.4%)
Abdominal pain upper	2/239 (0.8%)
Colitis	4/239 (1.7%)
Diarrhoea	5/239 (2.1%)
Diverticulum intestinal haemorrhagic	1/239 (0.4%)
Dysphagia	1/239 (0.4%)
Gastric haemorrhage	1/239 (0.4%)
Gastrointestinal haemorrhage	1/239 (0.4%)
Gastrointestinal oedema	1/239 (0.4%)
Ileus	2/239 (0.8%)
Inguinal hernia	1/239 (0.4%)
Intestinal obstruction	1/239 (0.4%)
Lower gastrointestinal haemorrhage	1/239 (0.4%)
Nausea	4/239 (1.7%)
Proctalgia	1/239 (0.4%)
Small intestinal obstruction	6/239 (2.5%)
Subileus	2/239 (0.8%)
Vomiting	4/239 (1.7%)
General disorders
Asthenia	2/239 (0.8%)
Fatigue	1/239 (0.4%)
General physical health deterioration	4/239 (1.7%)
Localised oedema	1/239 (0.4%)
Non-cardiac chest pain	1/239 (0.4%)
Pain	1/239 (0.4%)
Peripheral swelling	1/239 (0.4%)
Pyrexia	2/239 (0.8%)
Sudden death	1/239 (0.4%)
Hepatobiliary disorders
Cholecystitis	3/239 (1.3%)
Hepatic lesion	1/239 (0.4%)
Immune system disorders
Anaphylactic reaction	1/239 (0.4%)
Infections and infestations
Bacteraemia	1/239 (0.4%)
Bronchitis	1/239 (0.4%)
Cellulitis	3/239 (1.3%)
Cholecystitis infective	1/239 (0.4%)
Device related infection	1/239 (0.4%)
Diarrhoea infectious	1/239 (0.4%)
Diverticulitis	2/239 (0.8%)
Enterocolitis infectious	1/239 (0.4%)
Erysipelas	1/239 (0.4%)
Febrile infection	1/239 (0.4%)
Fungaemia	1/239 (0.4%)
Gastroenteritis	1/239 (0.4%)
Herpes zoster	2/239 (0.8%)
Infectious pleural effusion	2/239 (0.8%)
Intervertebral discitis	1/239 (0.4%)
Pelvic abscess	1/239 (0.4%)
Perinephric abscess	1/239 (0.4%)
Pharyngitis streptococcal	1/239 (0.4%)
Pneumonia	7/239 (2.9%)
Renal abscess	1/239 (0.4%)
Sepsis	8/239 (3.3%)
Septic shock	2/239 (0.8%)
Skin infection	1/239 (0.4%)
Urinary tract infection	3/239 (1.3%)
Urosepsis	1/239 (0.4%)
Injury, poisoning and procedural complications
Humerus fracture	1/239 (0.4%)
Post procedural fever	1/239 (0.4%)
Investigations
Blood creatinine increased	2/239 (0.8%)
C-reactive protein increased	1/239 (0.4%)
Transaminases increased	1/239 (0.4%)
Metabolism and nutrition disorders
Decreased appetite	1/239 (0.4%)
Dehydration	5/239 (2.1%)
Diabetes mellitus	1/239 (0.4%)
Hypokalaemia	1/239 (0.4%)
Hypomagnesaemia	1/239 (0.4%)
Hypovolaemia	1/239 (0.4%)
Lactic acidosis	1/239 (0.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/239 (0.8%)
Back pain	3/239 (1.3%)
Flank pain	1/239 (0.4%)
Musculoskeletal chest pain	1/239 (0.4%)
Myositis	1/239 (0.4%)
Neck pain	1/239 (0.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenoid cystic carcinoma	1/239 (0.4%)
Brain neoplasm	1/239 (0.4%)
Infected neoplasm	1/239 (0.4%)
Malignant neoplasm of cornea	1/239 (0.4%)
Malignant neoplasm progression	58/239 (24.3%)
Mesothelioma	2/239 (0.8%)
Neoplasm progression	2/239 (0.8%)
Penis carcinoma metastatic	1/239 (0.4%)
Squamous cell carcinoma	1/239 (0.4%)
Transitional cell carcinoma	1/239 (0.4%)
Tumour haemorrhage	1/239 (0.4%)
Tumour pain	4/239 (1.7%)
Nervous system disorders
Brain oedema	1/239 (0.4%)
Cerebellar infarction	1/239 (0.4%)
Cerebral infarction	1/239 (0.4%)
Cerebrovascular accident	2/239 (0.8%)
Facial paralysis	1/239 (0.4%)
Headache	1/239 (0.4%)
Intracranial mass	1/239 (0.4%)
Neuritis cranial	1/239 (0.4%)
Spinal cord compression	1/239 (0.4%)
Psychiatric disorders
Delirium	1/239 (0.4%)
Mental status changes	1/239 (0.4%)
Renal and urinary disorders
Acute kidney injury	4/239 (1.7%)
Chronic kidney disease	1/239 (0.4%)
Haematuria	1/239 (0.4%)
Hydronephrosis	1/239 (0.4%)
Renal failure	2/239 (0.8%)
Urinary tract obstruction	2/239 (0.8%)
Reproductive system and breast disorders
Vaginal haemorrhage	2/239 (0.8%)
Vulvovaginal pain	1/239 (0.4%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	3/239 (1.3%)
Bronchostenosis	1/239 (0.4%)
Dyspnoea	5/239 (2.1%)
Hypoxia	1/239 (0.4%)
Laryngeal haemorrhage	1/239 (0.4%)
Pleural effusion	4/239 (1.7%)
Pneumothorax	1/239 (0.4%)
Pulmonary embolism	1/239 (0.4%)
Pulmonary hypertension	1/239 (0.4%)
Respiratory failure	1/239 (0.4%)
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/239 (0.4%)
Vascular disorders
Embolism	1/239 (0.4%)
Venous stenosis	1/239 (0.4%)
Other (Not Including Serious) Adverse Events
	Advanced Malignancies Cohort
	Affected / at Risk (%)	# Events
Total	216/239 (90.4%)
Blood and lymphatic system disorders
Anaemia	41/239 (17.2%)
Endocrine disorders
Hypothyroidism	21/239 (8.8%)
Gastrointestinal disorders
Abdominal pain	33/239 (13.8%)
Abdominal pain upper	12/239 (5%)
Constipation	50/239 (20.9%)
Diarrhoea	52/239 (21.8%)
Dry mouth	14/239 (5.9%)
Nausea	53/239 (22.2%)
Vomiting	32/239 (13.4%)
General disorders
Chills	14/239 (5.9%)
Fatigue	90/239 (37.7%)
Oedema peripheral	24/239 (10%)
Pyrexia	24/239 (10%)
Infections and infestations
Upper respiratory tract infection	17/239 (7.1%)
Urinary tract infection	22/239 (9.2%)
Investigations
Alanine aminotransferase increased	16/239 (6.7%)
Aspartate aminotransferase increased	18/239 (7.5%)
Blood alkaline phosphatase increased	12/239 (5%)
Blood creatinine increased	15/239 (6.3%)
Weight decreased	22/239 (9.2%)
Metabolism and nutrition disorders
Decreased appetite	37/239 (15.5%)
Dehydration	23/239 (9.6%)
Hypokalaemia	18/239 (7.5%)
Hyponatraemia	15/239 (6.3%)
Hypophosphataemia	12/239 (5%)
Musculoskeletal and connective tissue disorders
Arthralgia	34/239 (14.2%)
Back pain	27/239 (11.3%)
Pain in extremity	15/239 (6.3%)
Nervous system disorders
Dizziness	15/239 (6.3%)
Headache	19/239 (7.9%)
Psychiatric disorders
Anxiety	13/239 (5.4%)
Insomnia	18/239 (7.5%)
Respiratory, thoracic and mediastinal disorders
Cough	43/239 (18%)
Dyspnoea	44/239 (18.4%)
Skin and subcutaneous tissue disorders
Dry skin	12/239 (5%)
Pruritus	26/239 (10.9%)
Rash	20/239 (8.4%)
Vascular disorders
Hypertension	17/239 (7.1%)

Limitations/Caveats

[Not Specified]

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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.