Phase II Study of Short Course FOLFOX Chemotherapy With E... | NCT04021108

Name	Class
Bristol-Myers Squibb	INDUSTRY

Description Module

Detailed Description

This is a randomized phase II study examining nivolumab alone versus radiation therapy with nivolumab in subjects who did not have disease progression to initial therapy with the combination of FOLFOX and Nivolumab. Subjects with advanced unresectable or metastatic gastroesophageal adenocarcinoma are eligible. All subjects will receive FOLFOX + nivolumab therapy. Subjects who demonstrate at least stable disease, as per RECIST 1.1, on their first imaging assessment at two months will receive one additional month of FOLFOX + nivolumab (3 months total), and then will be randomly assigned at a 1:1 ratio to receive either nivolumab alone or nivolumab plus radiation therapy. Radiation therapy fields and technique will be approved by central review. Radiation will be planned at 4Gy x 5 doses (20 Gy total), given concurrently with nivolumab. After 4 months of therapy, patients who remain on study will receive nivolumab 480 mg every 4 weeks. Subjects will be on study (intervention + follow-up) for approximately 24 months. The projected end date of the study, including data analysis, is February 2026.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cohort 1	Other	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks)	Drug: Nivolumab 240 MG
Cohort 2	Experimental	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions)	Drug: Nivolumab 240 MG

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Nivolumab 240 MG	Drug	Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.

Measure	Description	Time Frame
Number of Patients With 12-month Progression Free Survival in Each Arm	This will be measured by number of patients without disease progression at 12 months in the two study arms (patients who receive nivolumab with radiation and those who receive nivolumab alone)	12 months

Measure	Description	Time Frame
Amongst All Randomized Subjects, the Number of Subjects That Achieved 12-month Progression Free Survival	This will be measured by the number of patients without disease progression at 12 months in all enrolled patients.	12 months
Amongst All Randomized Subjects, Overall Survival, as Measured by the Rate of Survival in Patients, at 1-year

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Subjects with a diagnosis of advanced unresectable or metastatic gastroesophageal adenocarcinoma (eg. gastric, gastroesophageal junction, and esophageal adenocarcinoma)
Be willing and able to provide written informed consent/assent for the trial
Age > 18 years
ECOG performance status ≤ 1
Absolute neutrophil count ≥ 1,500/mL
Platelets ≥ 100,000/mL
Total bilirubin ≤ 1.5x upper limits of normal, unless the patient has known Gilbert's disease.
AST/ALT ≤ 2.5 upper limits of normal, or < 5x ULN for subjects with liver metastases
Creatinine ≤ 1.5 mg/dl. If Creatinine > 1.5 mg/dl, creatinine clearance > 60 ml/min
Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 28 days prior to initiation of treatment on Day 1.
For all males and females of childbearing potential, they should be agreeable to use an adequate method of contraception or birth control. For females of child bearing potential, a negative pregnancy test within 7 days of start of study drug is required

Exclusion Criteria

Prior cytotoxic therapy for metastatic or incurable disease.
Patients may have had prior therapy with curative intent for localized disease, if their recurrence or disease progression was more than six months from completing prior therapy.
HER2 positive adenocarcinoma
Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Known history of active TB (Bacillus Tuberculosis)
Known additional malignancy that is active. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Previous invasive malignancy treated with curative intent less than 3 years from time of registration. Exceptions include prostate cancer or basal cell skin cancer.
Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Known history of, or any evidence of active, non-infectious pneumonitis.
Active infection requiring systemic therapy.
History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
Has received a live vaccine within 30 days of planned start of study therapy.

Name	Affiliation	Role
Manish Shah, MD	Weill Medical College of Cornell University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Moffitt Cancer Center		Tampa	Florida	33612	United States
Washington University School of Medicine

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cohort 1	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jun 14, 2022

Arm/Group Information

ID	Title	Description
BG000	Cohort 1	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.
BG001	Cohort 2	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00033 BG00134 BG00267

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Patients With 12-month Progression Free Survival in Each Arm

This will be measured by number of patients without disease progression at 12 months in the two study arms (patients who receive nivolumab with radiation and those who receive nivolumab alone)

Posted

Count of Participants

Participants

12 months

ID	Title	Description
OG000	Cohort 1	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.
OG001	Cohort 2	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.

Units	Counts
Participants	OG00033 OG00134

Title

Denominators

Categories

Title	Measurements
	OG0009 OG0014

Secondary

Amongst All Randomized Subjects, the Number of Subjects That Achieved 12-month Progression Free Survival

This will be measured by the number of patients without disease progression at 12 months in all enrolled patients.

Per protocol section 11.1, this outcome measure will be reported for both randomized arms combined.

Posted

Count of Participants

Participants

12 months

ID	Title	Description
OG000	All Patients	All randomized patients evaluable per Arms A and B.

Units	Counts
Participants	OG00067

Secondary

Amongst All Randomized Subjects, Overall Survival, as Measured by the Rate of Survival in Patients, at 1-year

In both study arms, we will examine the rate of survival in patients over time from registration through their treatment

Posted

Number

percentage of patients

1 year

ID	Title	Description
OG000	Cohort 1:	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.
OG001	Cohort 2:	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.

Secondary

Occurrence of Significant Toxicity, as Measured by Rate of Grade 3 and Grade 4 Adverse Events (Combined) Attributable to Immunotherapy Per the Study Cohort

We will measure the rate of grade 3 or 4 adverse events attributable to immunotherapy in both study arms

Posted

Number

percentage of patients

2 year

ID	Title	Description
OG000	Cohort 1	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.
OG001	Cohort 2	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort 1	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 1 will receive Nivolumab alone (every 2 weeks for two doses, and then every 4 weeks) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.	23	33	18	33	22	33
EG001	Cohort 2	Subjects will receive standard dose FOLFOX plus nivolumab 240mg IV every 2 weeks for 2 months. If you are responding to treatment, you will receive FOLFOX plus nivolumab for one additional month and then you will be randomized to Cohort 1 or Cohort 2. Subjects in Cohort 2 will receive Nivolumab (every 2 weeks for two doses, and then every 4 weeks) plus radiation therapy (total 5 sessions) Nivolumab 240 MG: Nivolumab (OpdivoTM) is a potent and highly selective humanized monoclonal antibody (mAB) designed to block the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Cancer cells are able to send a signal to the PD-1 via the PD-L1 molecule, tricking the T-cell into recognizing the cancer cell as normal. Nivolumab is designed to disrupt that signal and expose the cancer cell to the immune system. Nivolumab is given intravenously over a 60-minute period, usually every two weeks.	28	34	18	34	23	34

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Adrenal Insufficiency	Endocrine disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0002 events2 affected33 at risk EG0011 events1 affected34 at risk
Alkaline phosphatase increased	Investigations	Systematic Assessment	EG0001 events1 affected33 at risk EG0011 events1 affected34 at risk
Allergic Reaction	Immune system disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Appetite decreased	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Ascites	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0002 events2 affected33 at risk EG0011 events1 affected34 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Atrial fibrillation	Cardiac disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Back pain	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0012 events2 affected34 at risk
Blood bilirubin increased	Investigations	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
COVID-19	Infections and infestations	Systematic Assessment	EG0002 events2 affected33 at risk EG0011 events1 affected34 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected33 at risk EG0010 events0 affected34 at risk
Dysphagia	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Aphasia	Nervous system disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0012 events2 affected34 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Esophageal hemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Esophageal obstruction	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Fatigue	General disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Febrile Neutropenia	Blood and lymphatic system disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Gastric hemorrhage	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0011 events1 affected34 at risk
Hypercalcemia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0003 events3 affected33 at risk EG0011 events1 affected34 at risk
Hypophysitis	Endocrine disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Hypotension	Vascular disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Hepatitis	Hepatobiliary disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
incarcerated hernia	General disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Infusion related reaction	General disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Lactic Acidosis	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0001 events1 affected33 at risk EG0011 events1 affected34 at risk
Mucositis oral	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0011 events1 affected34 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0014 events2 affected34 at risk
Neutrophil count decreased	Investigations	Systematic Assessment	EG00012 events8 affected33 at risk EG0016 events4 affected34 at risk
Chest Pain	General disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0013 events2 affected34 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Sepsis	Infections and infestations	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Sick sinus syndrome	Cardiac disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Stroke	Nervous system disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Supraventricular tachycardia	Cardiac disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Abscess	Infections and infestations	Systematic Assessment	EG0001 events1 affected33 at risk EG0010 events0 affected34 at risk
Syncope	General disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0011 events1 affected34 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected33 at risk EG0014 events2 affected34 at risk
Weight Loss	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected33 at risk EG0012 events2 affected34 at risk
White blood cell decreased	Investigations	Systematic Assessment	EG0002 events2 affected33 at risk EG0010 events0 affected34 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	Systematic Assessment	EG00028 events16 affected33 at risk EG00129 events16 affected34 at risk
Fatigue	General disorders	Systematic Assessment	EG00023 events16 affected33 at risk EG00129 events19 affected34 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG00015 events11 affected33 at risk EG00117 events12 affected34 at risk
Neutrophil Count Decreased	Investigations	Systematic Assessment	EG00031 events15 affected33 at risk EG00125 events15 affected34 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG00022 events14 affected33 at risk EG00121 events11 affected34 at risk
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG00017 events8 affected33 at risk EG00116 events6 affected34 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG00020 events9 affected33 at risk EG00116 events6 affected34 at risk
Peripheral sensory neuropathy	Nervous system disorders	Systematic Assessment	EG0008 events4 affected33 at risk EG00113 events8 affected34 at risk
Alkaline phosphatase increased	Investigations	Systematic Assessment	EG00014 events7 affected33 at risk EG00112 events6 affected34 at risk
Weight Loss	Metabolism and nutrition disorders	Systematic Assessment	EG00015 events7 affected33 at risk EG0017 events6 affected34 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG00015 events7 affected33 at risk EG0016 events3 affected34 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	Systematic Assessment	EG00017 events8 affected33 at risk EG0013 events3 affected34 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG00012 events5 affected33 at risk EG0018 events4 affected34 at risk
Platelet Count Decreased	Investigations	Systematic Assessment	EG0009 events5 affected33 at risk EG0018 events5 affected34 at risk
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0007 events5 affected33 at risk EG0019 events8 affected34 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG00010 events5 affected33 at risk EG0016 events5 affected34 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0005 events5 affected33 at risk EG00111 events10 affected34 at risk
Dysesthesia	Nervous system disorders	Systematic Assessment	EG0007 events7 affected33 at risk EG0019 events7 affected34 at risk
White blood cell count decreased	Investigations	Systematic Assessment	EG0009 events4 affected33 at risk EG0017 events4 affected34 at risk
Dysphagia	Gastrointestinal disorders	Systematic Assessment	EG0004 events4 affected33 at risk EG00111 events5 affected34 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG00011 events4 affected33 at risk EG0014 events2 affected34 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0007 events6 affected33 at risk EG0017 events7 affected34 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG00011 events11 affected33 at risk EG0012 events2 affected34 at risk
Mucositis oral	Gastrointestinal disorders	Systematic Assessment	EG00011 events7 affected33 at risk EG0012 events2 affected34 at risk
Headache	Nervous system disorders	Systematic Assessment	EG00010 events3 affected33 at risk EG0013 events2 affected34 at risk
Pyrexia	General disorders	Systematic Assessment	EG0008 events4 affected33 at risk EG0014 events4 affected34 at risk
Dyspepsia	Gastrointestinal disorders	Systematic Assessment	EG0009 events7 affected33 at risk EG0013 events1 affected34 at risk
Hiccups	Gastrointestinal disorders	Systematic Assessment	EG0005 events3 affected33 at risk EG0016 events6 affected34 at risk
Albumin decreased	Investigations	Systematic Assessment	EG0009 events4 affected33 at risk EG0012 events1 affected34 at risk
Paresthesia	Nervous system disorders	Systematic Assessment	EG0005 events5 affected33 at risk EG0015 events5 affected34 at risk
Hypokalemia	Metabolism and nutrition disorders	Systematic Assessment	EG0005 events2 affected33 at risk EG0015 events3 affected34 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0004 events3 affected33 at risk EG0016 events5 affected34 at risk
Edema limb	General disorders	Systematic Assessment	EG0004 events2 affected33 at risk EG0015 events3 affected34 at risk
Abdominal Distension	Gastrointestinal disorders	Systematic Assessment	EG0009 events5 affected33 at risk EG0011 events1 affected34 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	Systematic Assessment	EG0004 events4 affected33 at risk EG0014 events4 affected34 at risk
Dysgeusia	Nervous system disorders	Systematic Assessment	EG0004 events4 affected33 at risk EG0014 events4 affected34 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0003 events2 affected33 at risk EG0014 events1 affected34 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0005 events2 affected33 at risk EG0011 events1 affected34 at risk
Hypothyroidism	Endocrine disorders	Systematic Assessment	EG0003 events3 affected33 at risk EG0013 events3 affected34 at risk
Hyperglycemia	Metabolism and nutrition disorders	Systematic Assessment	EG0004 events4 affected33 at risk EG0011 events1 affected34 at risk

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins