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NCT03264404

Azacitidine and Pembrolizumab in Pancreatic Cancer

Completed Phase 2 Results posted Last updated 27 January 2026
What this trial tests

Phase 2 trial testing Pembrolizumab in Pancreas Cancer in 36 participants. Completed in 3 December 2024.

Timeline
1 October 2017
Primary endpoint
1 October 2021
3 December 2024

Quick facts

Lead sponsorSusan E. Bates
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment36
Start date1 October 2017
Primary completion1 October 2021
Estimated completion3 December 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Susan E. Bates

Who can join

18 and older, any sex, with Pancreas Cancer. 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.

Progression-Free Survival (PFS) Primary · 24 months

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.

GroupValue95% CI
Pembrolizumab1.491.38 – 1.74
Objective Response Rate (ORR) Secondary · Throughout study duration, up to approx 80 months

ORR is defined as the percentage of the participants in the analysis population who have a complete response (CR) or partial response (PR). Responses are based on assessments per RECIST 1.1.

GroupValue95% CI
Pembrolizumab9.7
Duration of Response (DOR) Secondary · Throughout study duration, up to approx 80 months

For subjects who demonstrate CR or PR, based on assessments per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.

Patient 1
GroupValue95% CI
Pembrolizumab2274
Patient 2
GroupValue95% CI
Pembrolizumab881
Patient 3
GroupValue95% CI
Pembrolizumab28
Disease Control Rate (DCR) Secondary · Throughout study duration, up to approx 80 months

DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments per RECIST 1.1.

GroupValue95% CI
Pembrolizumab35.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Throughout study duration, up to approx 80 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab
Serious: 9/36 (25%)
Deaths: 26/36

Serious adverse events (19 terms)

ReactionSystemPembrolizumab
DyspneaRespiratory, thoracic and mediastinal disorders
Gastric hemorrhageGeneral disorders
Abdominal painGastrointestinal disorders
Endocrine disordersEndocrine disorders
Nervous system disordersNervous system disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
PneumonitisRespiratory, thoracic and mediastinal disorders
StrokeNervous system disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
SepsisInfections and infestations
MyocarditisCardiac disorders
Hepatobiliary disordersHepatobiliary disorders
Vascular disordersVascular disorders
GastroparesisGastrointestinal disorders
Hepatic hemorrhageHepatobiliary disorders
AscitesGastrointestinal disorders
AnemiaBlood and lymphatic system disorders
Thromboembolic eventVascular disorders
Portal vein thrombosisHepatobiliary disorders
Other adverse events (84 terms — click to expand)

ReactionSystemPembrolizumab
DiarrheaGastrointestinal disorders
ConstipationGastrointestinal disorders
Abdominal PainGastrointestinal disorders
AnorexiaMetabolism and nutrition disorders
FatigueGeneral disorders
Alkaline phosphatase increasedInvestigations
Blood bilirubin increasedInvestigations
BloatingGastrointestinal disorders
Injection site reactionGeneral disorders
DyspneaRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
Infections and infestationsInfections and infestations
VomitingGastrointestinal disorders
Alanine aminotransferase increaseInvestigations
HyponatremiaInvestigations
Aspartate aminotransferase increasedInvestigations
Thromboembolic eventVascular disorders
ChillsGeneral disorders
AnemiaBlood and lymphatic system disorders
Weight lossInvestigations
HyperkalemiaInvestigations
PainGeneral disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
HypokalemiaInvestigations
HoarsenessRespiratory, thoracic and mediastinal disorders
Metabolism and nutrition disordersMetabolism and nutrition disorders
PruritusSkin and subcutaneous tissue disorders
Gastrointestinal disorderGastrointestinal disorders
AscitesGastrointestinal disorders
HypoalbuminemiaInvestigations
Flu like symptomsGeneral disorders
Back painMusculoskeletal and connective tissue disorders
Skin and subcutaneous tissue disorderSkin and subcutaneous tissue disorders
FeverGeneral disorders
Platelet count decreasedInvestigations
Acute kidney injuryRenal and urinary disorders
AnxietyPsychiatric disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Mucositis oralGastrointestinal disorders
Edema, LimbsGeneral disorders

Most-reported serious reactions: Dyspnea, Gastric hemorrhage, Abdominal pain, Endocrine disorders, Nervous system disorders, Respiratory failure, Pneumonitis, Stroke.

Data from ClinicalTrials.gov NCT03264404 adverse events section.

Sponsor's own description

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.

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. 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
  3. Chemokines Modulate Immune Surveillance in Tumorigenesis, Metastasis, and Response to Immunotherapy.
    Vilgelm AE, Richmond A. · · 2019 · cited 310× · PMID 30873179 · DOI 10.3389/fimmu.2019.00333
  4. 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
  5. Epigenetic modulation of antitumor immunity for improved cancer immunotherapy.
    Dai E, Zhu Z, Wahed S, Qu Z, et al · · 2021 · cited 224× · PMID 34930302 · DOI 10.1186/s12943-021-01464-x
  6. Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends.
    Nepali K, Liou JP. · · 2021 · cited 122× · PMID 33840388 · DOI 10.1186/s12929-021-00721-x
  7. New Treatment Strategies for Metastatic Pancreatic Ductal Adenocarcinoma.
    Singh RR, O'Reilly EM. · · 2020 · cited 119× · PMID 32306207 · DOI 10.1007/s40265-020-01304-0
  8. Advances in epigenetic therapeutics with focus on solid tumors.
    Jin N, George TL, Otterson GA, Verschraegen C, et al · · 2021 · cited 87× · PMID 33879235 · DOI 10.1186/s13148-021-01069-7

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