A Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Completed
• CT.gov ID: NCT03250273
• Collaborator: Syndax Pharmaceuticals (Industry), Bristol-Myers Squibb (Industry), National Cancer Institute (NCI) (NIH)
• Enrollment: 44
• Location: 1
• Arms: 2
• Actual Duration (Months): 36.5
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The proposed study is an open-label, two-arm study of entinostat plus nivolumab in patients with unresectable or metastatic cholangiocarcinoma (CCA) or pancreatic ductal adenocarcinoma (PDAC).

Condition or Disease	Intervention/Treatment	Phase
Metastatic Cholangiocarcinoma; Cholangiocarcinoma; Pancreatic Cancer; Metastatic Pancreatic Cancer; Unresectable Pancreatic Cancer; Unresectable Cholangiocarcinoma	Drug: Entinostat; Drug: Nivolumab; Drug: Entinostat; Drug: Nivolumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 44 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Clinical Trial of Entinostat in Combination With Nivolumab for Patients With Previously Treated Unresectable or Metastatic Cholangiocarcinoma and Pancreatic Adenocarcinoma
• Actual Study Start Date: Nov 6, 2017
• Actual Primary Completion Date: Nov 20, 2020
• Actual Study Completion Date: Nov 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm A - Cholangiocarcinoma	Drug: 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).; Other Names: SNDX-275 ; Drug: 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).; Other Names: OPDIVO, BMS-936558, MDX1106, ONO-4538
Experimental: ARM B - Pancreatic Cancer	Drug: 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).; Other Names: SNDX-275 ; Drug: 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).; Other Names: OPDIVO, BMS-936558, MDX1106, ONO-4538

Outcome Measures

Primary Outcome Measures

1. Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) [27 months]

   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.

Secondary Outcome Measures

1. Number of Patients Experiencing a Grade 3 or Above Treatment-related Adverse Event (AE) [29 months]

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

2. Overall Survival (OS) [38 months]

   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.

3. Overall Survival (OS) at 6 Months [6 months]

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

4. Overall Survival (OS) at 12 Months [12 months]

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

5. Overall Survival (OS) at 24 Months [24 months]

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

6. Overall Survival (OS) at 36 Months [36 months]

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

7. Duration of Response (DOR) [27 months]

   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.

8. Progression Free Survival (PFS) at 6 Months [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.

9. Progression Free Survival (PFS) at 12 Months [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.

10. Progression Free Survival (PFS) at 24 Months [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.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

1. Age ≥18 years.

2. Have histologically or cytologically proven cholangiocarcinoma or adenocarcinoma of the pancreas that is metastatic or unresectable.

3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

4. Life expectancy of greater than 12 weeks.

5. Patients must have adequate organ and marrow function defined by study-specified laboratory tests.

6. Woman of child bearing potential must have a negative pregnancy test.

7. Must have progressive measurable disease.

8. Must have an accessible non-bone tumor that can be biopsied.

9. Must use acceptable form of birth control while on study.

10. Willing to provide tissue and blood samples.

11. Ability to understand and willingness to sign a written informed consent document.

Exclusion Criteria:

1. Chemotherapy, radiotherapy, investigational therapy, or surgery less than 3 weeks prior to trial registration

2. Prior treatment with epigenetic therapy (such as entinostat, panobinostat, vorinostat, romidepsin, 5-azacitidine, or decitabine)

3. Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).

4. Hypersensitivity reaction to any monoclonal antibody.

5. 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).

6. Have significant and/or malignant pleural effusion

7. Has a pulse oximetry < 92% on room air.

8. Known history or evidence of brain metastases.

9. 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.

10. Are pregnant or breastfeeding.

11. Infection with HIV or hepatitis B or C.

12. Patients on immunosuppressive agents.

13. Requiring concurrent administration of valproic acid.

14. Patients with diverticulitis, intra-abdominal abscess, or GI obstruction

15. Any contraindication to oral agents.

16. Another active malignancy ≤ 3 years prior to registration with the exception of non-melanotic skin cancer or carcinoma-in-situ of any type.

17. Unwilling or unable to follow the study schedule for any reason.

18. Evidence of ascites on imaging.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21231

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Syndax Pharmaceuticals
• Bristol-Myers Squibb
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Nilofer Azad, MD, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 21, 2020

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT03250273
• Other Study ID Numbers: J1798; IRB00142149; 5P01CA247886
• First Posted: Aug 15, 2017
• Last Update Posted: Aug 16, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: Immunotherapy; Nivolumab; Entinostat; Pancreatic Adenocarcinoma; Cholangiocarcinoma; Unresectable; Metastatic; PD-1; Antibody
• Additional relevant MeSH terms: Adenocarcinoma; Pancreatic Neoplasms; Cholangiocarcinoma; Nivolumab; Entinostat

Study Results

Participant Flow

Pre-assignment Detail	1 enrolled participant withdrew consent prior to initiating treatment

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Period Title: Overall Study
STARTED	13	30
COMPLETED	11	18
NOT COMPLETED	2	12

Baseline Characteristics

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer	Total
Arm/Group Description	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).	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).	Total of all reporting groups
Overall Participants	13	30	43
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 76.9%	16 53.3%	26 60.5%
>=65 years	3 23.1%	14 46.7%	17 39.5%
Sex: Female, Male (Count of Participants)
Female	4 30.8%	13 43.3%	17 39.5%
Male	9 69.2%	17 56.7%	26 60.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 7.7%	1 3.3%	2 4.7%
Not Hispanic or Latino	11 84.6%	27 90%	38 88.4%
Unknown or Not Reported	1 7.7%	2 6.7%	3 7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 6.7%	2 4.7%
White	12 92.3%	28 93.3%	40 93%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 7.7%	0 0%	1 2.3%
Region of Enrollment (Count of Participants)
United States	13 100%	30 100%	43 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1)
Description	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.
Time Frame	27 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	11	18
Count of Participants [Participants]	0 0%	3 10%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Count of Participants [Participants]	5 38.5%	19 63.3%

3. Secondary Outcome

Title	Overall Survival (OS)
Description	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.
Time Frame	38 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Median (95% Confidence Interval) [months]	6.378	3.945

4. Secondary Outcome

Title	Overall Survival (OS) at 6 Months
Description	OS is defined as the proportion of subjects who are alive at 6 months. Estimation based on the Kaplan-Meier curve.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Number (95% Confidence Interval) [proportion of participants]	0.538 4.1%	0.311 1%

5. Secondary Outcome

Title	Overall Survival (OS) at 12 Months
Description	OS is defined as the proportion of subjects who are alive at 12 months. Estimation based on the Kaplan-Meier curve.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Number (95% Confidence Interval) [proportion of participants]	0.308 2.4%	0.173 0.6%

6. Secondary Outcome

Title	Overall Survival (OS) at 24 Months
Description	OS is defined as the proportion of subjects who are alive at 24 months. Estimation based on the Kaplan-Meier curve.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Number (95% Confidence Interval) [proportion of participants]	0.077 0.6%	0.035 0.1%

7. Secondary Outcome

Title	Overall Survival (OS) at 36 Months
Description	OS is defined as the proportion of subjects who are alive at 36 months. Estimation based on the Kaplan-Meier curve.
Time Frame	36 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Number (95% Confidence Interval) [proportion of participants]	0.077 0.6%	0.035 0.1%

8. Secondary Outcome

Title	Duration of Response (DOR)
Description	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.
Time Frame	27 months

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	0	3
Median (Full Range) [months]	10.2

9. Secondary Outcome

Title	Progression Free Survival (PFS) at 6 Months
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Number (95% Confidence Interval) [proportion of participants]	0 0%	0.1 0.3%

10. Secondary Outcome

Title	Progression Free Survival (PFS) at 12 Months
Description	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.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Number (95% Confidence Interval) [proportion of participants]	0 0%	0.1 0.3%

11. Secondary Outcome

Title	Progression Free Survival (PFS) at 24 Months
Description	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.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Arm/Group Description	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).	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).
Measure Participants	13	30
Number (95% Confidence Interval) [proportion of participants]	0 0%	0 0%

Adverse Events

Time Frame	29 months
Adverse Event Reporting Description	Adverse reporting collection was conducted by regular investigator assessment and laboratory measurements.
Arm/Group Title	Arm A - Cholangiocarcinoma		ARM B - Pancreatic Cancer
Arm/Group Description	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).		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).
All Cause Mortality
	Arm A - Cholangiocarcinoma		ARM B - Pancreatic Cancer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/13 (0%)		1/30 (3.3%)
Serious Adverse Events
	Arm A - Cholangiocarcinoma		ARM B - Pancreatic Cancer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/13 (38.5%)		4/30 (13.3%)
Gastrointestinal disorders
Colitis	1/13 (7.7%)	1	1/30 (3.3%)	1
General disorders
Fever	0/13 (0%)	0	1/30 (3.3%)	1
Infections and infestations
Pneumonia	1/13 (7.7%)	1	0/30 (0%)	0
Pneumonitis	3/13 (23.1%)	3	0/30 (0%)	0
Infection, unknown source	0/13 (0%)	0	1/30 (3.3%)	1
Investigations
Transaminitis	1/13 (7.7%)	1	0/30 (0%)	0
Metabolism and nutrition disorders
Renal tubular acidosis	0/13 (0%)	0	1/30 (3.3%)	1
Musculoskeletal and connective tissue disorders
Arthritis	0/13 (0%)	0	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	Arm A - Cholangiocarcinoma		ARM B - Pancreatic Cancer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/13 (92.3%)		26/30 (86.7%)
Blood and lymphatic system disorders
Anemia	1/13 (7.7%)	1	9/30 (30%)	9
Endocrine disorders
Hypothyroidism	1/13 (7.7%)	1	0/30 (0%)	0
Gastrointestinal disorders
Constipation	2/13 (15.4%)	2	0/30 (0%)	0
Diarrhea	2/13 (15.4%)	2	3/30 (10%)	3
Dry lips	1/13 (7.7%)	1	0/30 (0%)	0
Early satiety	1/13 (7.7%)	1	0/30 (0%)	0
Dry mouth	0/13 (0%)	0	2/30 (6.7%)	2
Mucositis oral	0/13 (0%)	0	4/30 (13.3%)	4
Nausea	6/13 (46.2%)	6	10/30 (33.3%)	10
Vomiting	6/13 (46.2%)	6	6/30 (20%)	6
General disorders
Chills	0/13 (0%)	0	2/30 (6.7%)	2
Edema	4/13 (30.8%)	4	4/30 (13.3%)	4
Fatigue	12/13 (92.3%)	12	19/30 (63.3%)	19
Fever	1/13 (7.7%)	1	2/30 (6.7%)	2
Flu-like symptoms	1/13 (7.7%)	1	0/30 (0%)	0
Infections and infestations
Thrush	2/13 (15.4%)	2	4/30 (13.3%)	4
Investigations
Aspartate aminotransferase increased	1/13 (7.7%)	1	0/30 (0%)	0
Lymphocyte count decreased	2/13 (15.4%)	2	8/30 (26.7%)	8
Neutrophil count decreased	1/13 (7.7%)	1	4/30 (13.3%)	4
Platelet count decreased	3/13 (23.1%)	3	3/30 (10%)	3
White blood cell decreased	1/13 (7.7%)	1	0/30 (0%)	0
Metabolism and nutrition disorders
Anorexia	5/13 (38.5%)	5	14/30 (46.7%)	14
Hypoalbuminemia	0/13 (0%)	0	3/30 (10%)	3
Hyponatremia	1/13 (7.7%)	1	5/30 (16.7%)	5
Weight loss	0/13 (0%)	0	2/30 (6.7%)	2
Nervous system disorders
Dizziness	1/13 (7.7%)	1	0/30 (0%)	0
Dysgeusia	2/13 (15.4%)	2	2/30 (6.7%)	2
Psychiatric disorders
Insomnia	1/13 (7.7%)	1	0/30 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	1/13 (7.7%)	1	0/30 (0%)	0
Rash maculo-papular	3/13 (23.1%)	3	0/30 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.