A Clinical Trial of Entinostat in Combination With Nivolu... | NCT03250273

NCT03250273

ID	Type	Description	Link
IRB00142149	Other Identifier	JHMI IRB
5P01CA247886	U.S. NIH Grant/Contract		View source

Status Module

Name	Class
Syndax Pharmaceuticals	INDUSTRY
Bristol-Myers Squibb	INDUSTRY
National Cancer Institute (NCI)	NIH

Label	Type	Description	Intervention Names
Arm A - Cholangiocarcinoma	Experimental		Drug: Entinostat Drug: Nivolumab
ARM B - Pancreatic Cancer	Experimental		Drug: Entinostat Drug: Nivolumab

Name	Type	Description	Arm Group Labels	Other Names
Entinostat	Drug	Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle).

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)	Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions. Subjects who discontinue due to clinical progression prior to post-baseline tumor assessments were considered as non-responders.	27 months

Secondary Outcomes

Measure	Description	Time Frame
Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE)	When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.	29 months
Overall Survival (OS)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Age ≥18 years.
Have histologically or cytologically proven cholangiocarcinoma or adenocarcinoma of the pancreas that is metastatic or unresectable.
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Life expectancy of greater than 12 weeks.
Patients must have adequate organ and marrow function defined by study-specified laboratory tests.
Woman of child bearing potential must have a negative pregnancy test.
Must have progressive measurable disease.
Must have an accessible non-bone tumor that can be biopsied.
Must use acceptable form of birth control while on study.
Willing to provide tissue and blood samples.
Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

Chemotherapy, radiotherapy, investigational therapy, or surgery less than 3 weeks prior to trial registration
Prior treatment with epigenetic therapy (such as entinostat, panobinostat, vorinostat, romidepsin, 5-azacitidine, or decitabine)
Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).
Hypersensitivity reaction to any monoclonal antibody.
History of any autoimmune disease: inflammatory bowel disease, (including ulcerative colitis and Crohn's Disease), rheumatoid arthritis, systemic progressive sclerosis (scleroderma), systemic lupus erythematosus (SLE) autoimmune vasculitis (e.g., Wegener's Granulomatosis), central nervous system (CNS) or motor neuropathy considered to be of autoimmune origin (e.g., Guillain-Barre Syndrome, Myasthenia Gravis, Multiple Sclerosis). Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event).
Have significant and/or malignant pleural effusion
Has a pulse oximetry < 92% on room air.
Known history or evidence of brain metastases.
Conditions, including alcohol or drug dependence, intercurrent illness, or lack of sufficient peripheral venous access, that would affect the patient's ability to comply with study visits and procedures.
Are pregnant or breastfeeding.
Infection with HIV or hepatitis B or C.
Patients on immunosuppressive agents.
Requiring concurrent administration of valproic acid.
Patients with diverticulitis, intra-abdominal abscess, or GI obstruction
Any contraindication to oral agents.
Another active malignancy ≤ 3 years prior to registration with the exception of non-melanotic skin cancer or carcinoma-in-situ of any type.
Unwilling or unable to follow the study schedule for any reason.
Evidence of ascites on imaging.

Name	Affiliation	Role
Nilofer Azad, MD	Johns Hopkins University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Sidney Kimmel Comprehensive Cancer Center		Baltimore	Maryland	21231	United States

PubMed Identifier	Type	Citation	Retractions
39532835	Derived	Baretti M, Danilova L, Durham JN, Betts CB, Cope L, Sidiropoulos DN, Tandurella JA, Charmsaz S, Gross N, Hernandez A, Ho WJ, Thoburn C, Walker R, Leatherman J, Mitchell S, Christmas B, Saeed A, Gaykalova DA, Yegnasubramanian S, Fertig EJ, Coussens LM, Yarchoan M, Jaffee E, Azad NS. Entinostat in combination with nivolumab in metastatic pancreatic ductal adenocarcinoma: a phase 2 clinical trial. Nat Commun. 2024 Nov 12;15(1):9801. doi: 10.1038/s41467-024-52528-7.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

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	May 21, 2020

Arm/Group Information

ID	Title	Description
BG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
BG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00013 BG00130 BG00243

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000 BG0010 BG0020
Between 18 and 65 years

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0004 BG00113 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00013 BG00130 BG002

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

Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)

Objective Response Rate (ORR) is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on RECIST 1.1 criteria. CR = disappearance of all target lesions, PR is =>30% decrease in sum of diameters of target lesions. Subjects who discontinue due to clinical progression prior to post-baseline tumor assessments were considered as non-responders.

Posted

Count of Participants

Participants

27 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Units	Counts
Participants	OG00013 OG00127

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0013

Secondary

Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE)

When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.

Posted

Count of Participants

Participants

29 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Units	Counts

Secondary

Overall Survival (OS)

OS is defined as the duration of time from start of study treatment to time of death (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis). Estimation based on the Kaplan-Meier curve.

Posted

Median

95% Confidence Interval

months

38 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Secondary

Overall Survival (OS) at 6 Months

OS is defined as the proportion of subjects who are alive at 6 months. Estimation based on the Kaplan-Meier curve.

Posted

Number

95% Confidence Interval

proportion of participants

6 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Units	Counts
Participants

Secondary

Overall Survival (OS) at 12 Months

OS is defined as the proportion of subjects who are alive at 12 months. Estimation based on the Kaplan-Meier curve.

Posted

Number

95% Confidence Interval

proportion of participants

12 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Units	Counts
Participants

Secondary

Overall Survival (OS) at 24 Months

OS is defined as the proportion of subjects who are alive at 24 months. Estimation based on the Kaplan-Meier curve.

Posted

Number

95% Confidence Interval

proportion of participants

24 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Units	Counts
Participants

Secondary

Overall Survival (OS) at 36 Months

OS is defined as the proportion of subjects who are alive at 36 months. Estimation based on the Kaplan-Meier curve.

Posted

Number

95% Confidence Interval

proportion of participants

36 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Units	Counts
Participants

Secondary

Duration of Response (DOR)

Duration of response (DOR) will be calculated for subjects who achieve a best overall response of CR or PR. DOR is defined as the number of months from the start date of PR or CR (whichever response is recorded first) and subsequently confirmed to the first date that recurrent or progressive disease or death is documented. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions.

There were no responses (PR or CR) observed in Arm A; therefore, the number of analyzed participants is zero. 3 participants achieved response in Arm B.

Posted

Median

Full Range

months

27 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Secondary

Progression Free Survival (PFS) at 6 Months

PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 6 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

Posted

Number

95% Confidence Interval

proportion of participants

6 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Secondary

Progression Free Survival (PFS) at 12 Months

PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 12 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

Posted

Number

95% Confidence Interval

proportion of participants

12 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Secondary

Progression Free Survival (PFS) at 24 Months

PFS is defined as the proportion of patients without disease progression (PD or relapse from CR) or death due to any cause at 24 months. Disease progression will be assessed using RECIST (version 1.1). Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.Estimation based on the Kaplan-Meier curve.

Posted

Number

95% Confidence Interval

proportion of participants

24 months

ID	Title	Description
OG000	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).
OG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

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	Arm A - Cholangiocarcinoma	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).	0	13	4	13	12	13
EG001	ARM B - Pancreatic Cancer	Entinostat: Entinostat (5mg) will be administered starting with 2 lead-in doses at 14 and 7 days before the first dose of nivolumab in combination with entinostat. After the lead-in dose, entinostat will be administered once a week (days 1, 8, 15, and 21 of each treatment cycle). Nivolumab: After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).	1	30	3	30	27	30

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Colitis	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected30 at risk
Pneumonia	Infections and infestations	Systematic Assessment	EG0002 events1 affected13 at risk EG0010 events0 affected30 at risk
Pneumonitis	Infections and infestations	Systematic Assessment	EG0002 events2 affected13 at risk EG0010 events0 affected30 at risk
Transaminitis	Investigations	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected30 at risk
Renal tubular acidosis	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected30 at risk
Arthritis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 events0 affected13 at risk EG0011 events1 affected30 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 events1 affected13 at risk EG00114 events9 affected30 at risk
Hypothyroidism	Endocrine disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected30 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected13 at risk EG0011 events1 affected30 at risk
Diarrhea	Gastrointestinal disorders	Systematic Assessment	EG0002 events2 affected13 at risk EG0014 events3 affected30 at risk
Dry lips	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected30 at risk
Early satiety	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0011 events1 affected30 at risk
Dry mouth	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected13 at risk EG0012 events2 affected30 at risk
Mucositis oral	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected13 at risk EG0015 events4 affected30 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0008 events6 affected13 at risk EG00111 events10 affected30 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0000 events0 affected13 at risk EG0017 events6 affected30 at risk
Chills	General disorders	Systematic Assessment	EG0000 events0 affected13 at risk EG0013 events2 affected30 at risk
Edema	General disorders	Systematic Assessment	EG0004 events4 affected13 at risk EG0014 events4 affected30 at risk
Fatigue	General disorders	Systematic Assessment	EG00018 events12 affected13 at risk EG00125 events20 affected30 at risk
Fever	General disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0017 events3 affected30 at risk
Flu-like symptoms	General disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected30 at risk
Thrush	Infections and infestations	Systematic Assessment	EG0002 events2 affected13 at risk EG0014 events4 affected30 at risk
Lymphocyte count decreased	Investigations	Systematic Assessment	EG0002 events2 affected13 at risk EG00115 events8 affected30 at risk
Neutrophil count decreased	Investigations	Systematic Assessment	EG0001 events1 affected13 at risk EG0016 events4 affected30 at risk
Platelet count decreased	Investigations	Systematic Assessment	EG0008 events3 affected13 at risk EG0014 events3 affected30 at risk
White blood cell decreased	Investigations	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected30 at risk
Anorexia	Metabolism and nutrition disorders	Systematic Assessment	EG0006 events5 affected13 at risk EG00117 events15 affected30 at risk
Hypoalbuminemia	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected13 at risk EG0016 events3 affected30 at risk
Hyponatremia	Metabolism and nutrition disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0015 events5 affected30 at risk
Weight loss	Metabolism and nutrition disorders	Systematic Assessment	EG0000 events0 affected13 at risk EG0012 events2 affected30 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected30 at risk
Dysgeusia	Nervous system disorders	Systematic Assessment	EG0002 events2 affected13 at risk EG0014 events2 affected30 at risk
Insomnia	Psychiatric disorders	Systematic Assessment	EG0001 events1 affected13 at risk EG0010 events0 affected30 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0007 events1 affected13 at risk EG0011 events1 affected30 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0004 events3 affected13 at risk EG00112 events4 affected30 at risk

ID	Term
D018281	Cholangiocarcinoma
D010190	Pancreatic Neoplasms
D009362	Neoplasm Metastasis

ID	Term
D000230	Adenocarcinoma
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D004701	Endocrine Gland Neoplasms
D004066	Digestive System Diseases
D010182	Pancreatic Diseases
D004700	Endocrine System Diseases
D009385	Neoplastic Processes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

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