NCT03250273

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

Completed Phase 2 Results posted Last updated 28 May 2025

What this trial tests

Phase 2 trial testing Entinostat in Metastatic Cholangiocarcinoma in 44 participants. Completed in 20 November 2020.

Timeline

6 November 2017

Primary endpoint
20 November 2020

20 November 2020

Quick facts

Lead sponsor	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	44
Start date	6 November 2017
Primary completion	20 November 2020
Estimated completion	20 November 2020
Sites	1 location across United States

Drugs / interventions tested

• Entinostat — full drug profile →
• Nivolumab (nivolumab) — full drug profile →
• Entinostat — full drug profile →
• Nivolumab (nivolumab) — full drug profile →

Conditions studied

• Metastatic Cholangiocarcinoma — all drugs for Metastatic Cholangiocarcinoma →
• Cholangiocarcinoma — all drugs for Cholangiocarcinoma →
• Pancreatic Cancer — all drugs for Pancreatic Cancer →
• Metastatic Pancreatic Cancer — all drugs for Metastatic Pancreatic Cancer →

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins — full company profile →

Who can join

18 and older, any sex, with Metastatic Cholangiocarcinoma or Cholangiocarcinoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Objective Response Rate (ORR) Using Response Evaluation Criteria for Solid Tumors (RECIST 1.1) Primary · 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. Subjects who discontinue due to clinical progression prior to post-baseline tumor assessments were considered as non-responders.

Group	Value	95% CI
Arm A - Cholangiocarcinoma	0
ARM B - Pancreatic Cancer	3

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

Group	Value	95% CI
Arm A - Cholangiocarcinoma	5
ARM B - Pancreatic Cancer	19

Overall Survival (OS) Secondary · 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.

Group	Value	95% CI
Arm A - Cholangiocarcinoma	6.378	3.748 – NA
ARM B - Pancreatic Cancer	2.729	1.84 – 5.62

Overall Survival (OS) at 6 Months Secondary · 6 months

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

Group	Value	95% CI
Arm A - Cholangiocarcinoma	0.538	0.326 – 0.891
ARM B - Pancreatic Cancer	0.277	0.153 – 0.498

Overall Survival (OS) at 12 Months Secondary · 12 months

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

Group	Value	95% CI
Arm A - Cholangiocarcinoma	0.308	0.136 – 0.695
ARM B - Pancreatic Cancer	0.138	0.056 – 0.343

Overall Survival (OS) at 24 Months Secondary · 24 months

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

Group	Value	95% CI
Arm A - Cholangiocarcinoma	0.077	0.012 – 0.506
ARM B - Pancreatic Cancer	0.035	0.005 – 0.237

Overall Survival (OS) at 36 Months Secondary · 36 months

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

Group	Value	95% CI
Arm A - Cholangiocarcinoma	0.077	0.012 – 0.506
ARM B - Pancreatic Cancer	0.035	0.005 – 0.237

Duration of Response (DOR) Secondary · 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.

Group	Value	95% CI
ARM B - Pancreatic Cancer	10.2	3.7 – 17.9

Progression Free Survival (PFS) at 6 Months Secondary · 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.

Group	Value	95% CI
Arm A - Cholangiocarcinoma	0	NA – NA
ARM B - Pancreatic Cancer	0.067	0.017 – 0.254

Progression Free Survival (PFS) at 12 Months Secondary · 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.

Group	Value	95% CI
Arm A - Cholangiocarcinoma	0	NA – NA
ARM B - Pancreatic Cancer	0.067	0.017 – 0.254

Progression Free Survival (PFS) at 24 Months Secondary · 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.

Group	Value	95% CI
Arm A - Cholangiocarcinoma	0	NA – NA
ARM B - Pancreatic Cancer	0	NA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: 29 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm A - Cholangiocarcinoma

Serious: 4/13 (31%)

Deaths: 0/13

ARM B - Pancreatic Cancer

Serious: 3/30 (10%)

Deaths: 1/30

Serious adverse events (6 terms)

Reaction	System	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Pneumonitis	Infections and infestations	—	—
Colitis	Gastrointestinal disorders	—	—
Pneumonia	Infections and infestations	—	—
Transaminitis	Investigations	—	—
Renal tubular acidosis	Metabolism and nutrition disorders	—	—
Arthritis	Musculoskeletal and connective tissue disorders	—	—

Other adverse events (29 terms — click to expand)

Reaction	System	Arm A - Cholangiocarcinoma	ARM B - Pancreatic Cancer
Fatigue	General disorders	—	—
Anorexia	Metabolism and nutrition disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Anemia	Blood and lymphatic system disorders	—	—
Lymphocyte count decreased	Investigations	—	—
Vomiting	Gastrointestinal disorders	—	—
Hyponatremia	Metabolism and nutrition disorders	—	—
Mucositis oral	Gastrointestinal disorders	—	—
Edema	General disorders	—	—
Thrush	Infections and infestations	—	—
Neutrophil count decreased	Investigations	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—
Diarrhea	Gastrointestinal disorders	—	—
Fever	General disorders	—	—
Platelet count decreased	Investigations	—	—
Hypoalbuminemia	Metabolism and nutrition disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Dry mouth	Gastrointestinal disorders	—	—
Chills	General disorders	—	—
Weight loss	Metabolism and nutrition disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Hypothyroidism	Endocrine disorders	—	—
Dry lips	Gastrointestinal disorders	—	—
Early satiety	Gastrointestinal disorders	—	—
Flu-like symptoms	General disorders	—	—
White blood cell decreased	Investigations	—	—
Dizziness	Nervous system disorders	—	—
Insomnia	Psychiatric disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—

Most-reported serious reactions: Pneumonitis, Colitis, Pneumonia, Transaminitis, Renal tubular acidosis, Arthritis.

Data from ClinicalTrials.gov NCT03250273 adverse events section.

Sponsor's own description

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).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.
   Cheng Y, He C, Wang M, Ma X, et al · · 2019 · cited 760× · PMID 31871779 · DOI 10.1038/s41392-019-0095-0
2. Myeloid-derived suppressor cells as immunosuppressive regulators and therapeutic targets in cancer.
   Li K, Shi H, Zhang B, Ou X, et al · · 2021 · cited 687× · PMID 34620838 · DOI 10.1038/s41392-021-00670-9
3. Challenges and Opportunities for Pancreatic Cancer Immunotherapy.
   Bear AS, Vonderheide RH, O'Hara MH. · · 2020 · cited 500× · PMID 32946773 · DOI 10.1016/j.ccell.2020.08.004
4. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
   Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
5. Epigenetic regulation in the tumor microenvironment: molecular mechanisms and therapeutic targets.
   Yang J, Xu J, Wang W, Zhang B, et al · · 2023 · cited 251× · PMID 37217462 · DOI 10.1038/s41392-023-01480-x
6. Current and emerging therapies for patients with advanced pancreatic ductal adenocarcinoma: a bright future.
   Christenson ES, Jaffee E, Azad NS. · · 2020 · cited 194× · PMID 32135117 · DOI 10.1016/s1470-2045(19)30795-8
7. Entinostat Converts Immune-Resistant Breast and Pancreatic Cancers into Checkpoint-Responsive Tumors by Reprogramming Tumor-Infiltrating MDSCs.
   Christmas BJ, Rafie CI, Hopkins AC, Scott BA, et al · · 2018 · cited 184× · PMID 30341213 · DOI 10.1158/2326-6066.cir-18-0070
8. Study and analysis of antitumor resistance mechanism of PD1/PD-L1 immune checkpoint blocker.
   Wang Z, Wu X. · · 2020 · cited 147× · PMID 32875727 · DOI 10.1002/cam4.3410