Azacitidine and Pembrolizumab in Pancreatic Cancer

NCT03264404 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAR3554
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the effectiveness of combining immune therapy, pembrolizumab, with a hypomethylating agent, azacitidine, for pancreatic cancer. People who have advanced pancreatic cancer with disease progression on first-line therapy are usually treated with a second chemotherapy regimen. However, there is no single accepted chemotherapy regimen and national guidelines recommend chemotherapy or clinical trial participation. In this study, all study subjects will receive a combination of immune therapy (every 3 weeks) and a hypomethylating agent (every 4 weeks). To date, studies have shown that combining a hypomethylating agent with chemotherapy or immune therapy may benefit patients across different solid tumor types including pancreatic cancer. Preclinical data in a mouse model of pancreatic cancer demonstrates improvement in survival with the combination of a hypomethylating agent and immune therapy. However, the use of single agent hypomethylating agent or immune therapy has not been shown to be effective in patients with pancreatic cancer. The one exception, to date, is the use of immune therapy in those individuals with a particular genetic feature known as mismatch repair deficiency and microsatellite instability. The combination of immune therapy and a hypomethylating agent has not been studied in human subjects and is not approved by the FDA for use in pancreatic cancer. This is a non-randomized, single-center, open-label trial of pembrolizumab and azacitidine in subjects with locally advanced or metastatic pancreatic adenocarcinoma. Approximately 31 individuals will be asked to participate in this study.

Conditions

Pancreas Cancer

Keywords

Pancreas; pembrolizumab; azacitidine; metastatic pancreatic cancer; first-line

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  PFS is defined as the time from the first day of trial treatment to the first documented disease progression per RECIST 1.1 (At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression)) or death due to any cause, whichever occurs first.

  24 months

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Throughout study duration, up to approx 80 months

• Duration of Response (DOR)

  Throughout study duration, up to approx 80 months

• Disease Control Rate (DCR)

  Throughout study duration, up to approx 80 months

Study Arms (1)

Pembrolizumab

EXPERIMENTAL

Patients with advanced pancreatic cancer will receive pembrolizumab with the hypomethylating agent azacitidine.

Drug: Pembrolizumab; Drug: Azacitidine

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg IV every 3 weeks until progression

Also known as: Keytruda

Pembrolizumab

Azacitidine DRUG

50 mg/m2 subcutaneous daily for 5 days every 28 days

Also known as: Vidaza

Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Be willing and able to provide written informed consent for the trial.
• Age ≥18 years of age on day of signing informed consent.
• Have confirmed diagnosis of pancreatic ductal adenocarcinoma
• Have a predicted life expectancy of greater than 3 months.
• Have measurable disease based on RECIST 1.1.
• Have a performance status of 0 or 1 using the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days of first dose of study drug.
• Have documented radiographic progression to or documented intolerance of first line systemic chemotherapy which included either gemcitabine or Fluorouracil (5-FU) based regimen (including capecitabine).
• Subjects who have documented disease recurrence within 6 months of completing neoadjuvant or adjuvant chemotherapy for limited disease will be eligible for study. Subjects who recur greater than 6 months after completing adjuvant or neoadjuvant chemotherapy will not be eligible unless they receive additional chemotherapy for advanced disease.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, or herbal/complementary oral or IV medicine within 2 weeks of the first dose of treatment.
• Has received chemotherapy or radiotherapy within 14 days of first dose of study medication.

Sponsors & Collaborators

• Susan E. Bates: lead

Study Sites (1)

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Related Publications (2)

• Safyan RA, White RA, Gonda TA, Lee SM, Han J, Kuriakose N, Yamamoto NK, Kugel S, Jamison JK, Manji GA, Schwartz GJ, Oberstein PE, Bates SE. Phase 2 Study of Azacitidine plus Pembrolizumab as Second-Line Treatment in Patients with Locally Advanced or Metastatic Pancreatic Ductal Adenocarcinoma. Oncologist. 2026 Mar 17:oyag091. doi: 10.1093/oncolo/oyag091. Online ahead of print.

  PMID: 41844546 DERIVED

• Tost J, Ak-Aksoy S, Campa D, Corradi C, Farinella R, Ibanez-Costa A, Dubrot J, Earl J, Melian EB, Kataki A, Kolnikova G, Madjarov G, Chaushevska M, Strnadel J, Tanic M, Tomas M, Dubovan P, Urbanova M, Buocikova V, Smolkova B. Leveraging epigenetic alterations in pancreatic ductal adenocarcinoma for clinical applications. Semin Cancer Biol. 2025 Feb;109:101-124. doi: 10.1016/j.semcancer.2025.01.003. Epub 2025 Jan 23.

  PMID: 39863139 DERIVED

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

pembrolizumab; Azacitidine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Susan E Bates, MD
• Organization: Columbia University

seb2227@cumc.columbia.edu

212-305-9422

Study Officials

• Susan E Bates, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine and Assistant Attending in Hematology / Oncology

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: August 29, 2017
• Study Start: October 1, 2017
• Primary Completion: October 1, 2021
• Study Completion: December 3, 2024
• Last Updated: January 27, 2026
• Results First Posted: July 5, 2023

Record last verified: 2026-01

Locations

US (1)