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

NCT03250273 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: J1798IRB001421495P01CA247886
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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).

Conditions

Metastatic Cholangiocarcinoma; Cholangiocarcinoma; Pancreatic Cancer; Metastatic Pancreatic Cancer; Unresectable Pancreatic Cancer; Unresectable Cholangiocarcinoma

Keywords

Immunotherapy; Nivolumab; Entinostat; Pancreatic Adenocarcinoma; Cholangiocarcinoma; Unresectable; Metastatic; PD-1; Antibody

Outcome Measures

Primary Outcomes (1)

• 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 (10)

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

  29 months

• Overall Survival (OS)

  38 months

• Overall Survival (OS) at 6 Months

  6 months

• Overall Survival (OS) at 12 Months

  12 months

• Overall Survival (OS) at 24 Months

  24 months

Study Arms (2)

Arm A - Cholangiocarcinoma

EXPERIMENTAL

Drug: Entinostat; Drug: Nivolumab

ARM B - Pancreatic Cancer

EXPERIMENTAL

Drug: Entinostat; Drug: Nivolumab

Interventions

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).

Also known as: SNDX-275

Arm A - Cholangiocarcinoma

Nivolumab DRUG

After both lead-in doses of entinostat, nivolumab (240 mg) will be administered every 2 weeks (day 1 and day 15 of a cycle).

Also known as: OPDIVO, BMS-936558, MDX1106, ONO-4538

Arm A - Cholangiocarcinoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21231, United States

Location

Related Publications (1)

• 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.

  PMID: 39532835 DERIVED

MeSH Terms

Conditions

Cholangiocarcinoma; Pancreatic Neoplasms; Neoplasm Metastasis

Interventions

entinostat; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Nilofer Azad, MD
• Organization: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

nazad2@jhmi.edu

410-614-9169

Study Officials

• Nilofer Azad, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2017
• First Posted: August 15, 2017
• Study Start: November 6, 2017
• Primary Completion: November 20, 2020
• Study Completion: November 20, 2020
• Last Updated: May 28, 2025
• Results First Posted: December 16, 2021

Record last verified: 2025-05

Locations

US (1)