Pancreas CancerPhase 2NCT03264404
Azacitidine and Pembrolizumab in Pancreatic Cancer
A Phase 2 study testing Pembrolizumab and Azacitidine in people with Pancreas Cancer, run by Susan E. Bates at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pancreas Cancer
- What is being tested?
- Pembrolizumab and Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2017to 3 Dec 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Phase II Open-Label, Single-Center Study Evaluating Safety and Efficacy of Pembrolizumab Following Induction With the Hypomethylating Agent Azacitidine in Patients With Advanced Pancreatic Cancer After Failure of First-Line Therapy
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.
Read the detailed description
Pancreatic ductal adenocarcinoma (PDA) has the worst prognosis of any major malignancy in the United States and, unlike other common cancers, annual deaths from PDA are rising. Despite recent advances, cytotoxic chemotherapy for PDA has been disappointing. Even among the small subset of patients who are suitable for surgical resection at the time of diagnosis, complete resection is followed by recurrence in majority of patients without further systemic therapy. Thus all PDA patients require systemic chemotherapy and more effective regimens are urgently needed.
Combination chemotherapy is effective in controlling disease and prolonging survival in patients with advanced pancreatic cancer. Despite recent successful phase 3 studies in the first-line setting, there is no defined second-line treatment for patients who experience disease progression following first-line therapy. Consensus guidelines (such as the National Comprehensive Cancer Network (NCCN) guidelines) recommend clinical trial participation in this setting.
The investigators' pre-clinical data suggests that decitabine treatment in the KPC model of pancreatic cancer leads to a significant up-regulation of interferon-related genes and a polarization of the infiltrating immune cells. Based on these results, the investigators have evaluated the effect of single agent decitabine or anti-PD1H (a homologue of PD1 with very similar function and expression pattern) compared to combination therapy (treatment with decitabine followed by PD1H blockade). The investigators' preliminary results showed minimal effect of either agent alone on tumor growth but marked decrease in tumor progression in the combination arm. These results form the foundation of this phase II study.
This study will treat patients with the combination of azacitidine and pembrolizumab. A direct comparison between azacitidine and decitabine in terms of efficacy within a controlled clinical trial has not been performed thus far. In randomized myelodysplastic syndrome (MDS) trials, the remission rates were similar for azacitidine and decitabine but the overall survival in the experimental arm was significantly shorter in the decitabine trial compared to the azacitidine trial. A primary reason to utilize azacitidine in this setting is our desire to amply reduced dose therapy with the goal of maintaining subjects on therapy Low-dose azacitidine is being tested in phase I/II clinical trials for advanced solid tumors-mainly colorectal cancer, small-cell lung carcinomas, ovarian cancer, and breast cancer.
- Conditions
- Pancreas Cancer
- Being tested
- Pembrolizumab, Azacitidine
- Keywords
- Pancreas, pembrolizumab, azacitidine, metastatic pancreatic cancer, first-line
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Also called Keytruda
Pembrolizumab 200 mg IV every 3 weeks until progression
AzacitidineDrug
Also called Vidaza
50 mg/m2 subcutaneous daily for 5 days every 28 days
| Study group | Role | What they receive |
|---|---|---|
| Pembrolizumab | Experimental | Patients with advanced pancreatic cancer will receive pembrolizumab with the hypomethylating agent azacitidine. Receives: Drug: Pembrolizumab; Drug: Azacitidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 24 months
Secondary outcomes (3)
Objective Response Rate (ORR)
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.
Measured: Throughout study duration, up to approx 80 months
Duration of Response (DOR)
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.
Measured: Throughout study duration, up to approx 80 months
Disease Control Rate (DCR)
DCR is defined as the percentage of participants who have achieved CR, PR, or stable disease (SD) based on assessments per RECIST 1.1.
Measured: Throughout study duration, up to approx 80 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2017
- Study start1 Oct 2017
- Primary completion1 Oct 2021
- Study completion3 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pancreas CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Susan E. Bates
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Susan E. Bates, Columbia University
- Investigators
- Susan E Bates, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03264404
- Sponsor's protocol ID
- AAAR3554
- Status last verified
- Jan 2026
- First submitted
- 22 Aug 2017
- Last updated
- 27 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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 9;31(4):oyag091. doi: 10.1093/oncolo/oyag091.
PubMed 41844546Tost 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.
PubMed 39863139
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Open-Label, Single-Center Study Evaluating Safety and Efficacy of Pembrolizumab Following Induction With the Hypomethylating Agent Azacitidine in Patients With Advanced Pancreatic Cancer After Failure of First-Line Therapy
- ClinicalTrials.gov ID
- NCT03264404
- Acronym / sponsor ID
- AAAR3554
- Conditions
- Pancreas Cancer
- Keywords
- Pancreas, pembrolizumab, azacitidine, metastatic pancreatic cancer, first-line
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Susan E. BatesUniversity, hospital or other
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 1 Oct 2021 (actual)
- Study completion
- 3 Dec 2024 (actual)
- First posted
- 29 Aug 2017 (actual)
- Results
- Posted 5 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Pancreatic ductal adenocarcinoma (PDA) has the worst prognosis of any major malignancy in the United States and, unlike other common cancers, annual deaths from PDA are rising. Despite recent advances, cytotoxic chemotherapy for PDA has been disappointing. Even among the small subset of patients who are suitable for surgical resection at the time of diagnosis, complete resection is followed by recurrence in majority of patients without further systemic therapy. Thus all PDA patients require systemic chemotherapy and more effective regimens are urgently needed.
Combination chemotherapy is effective in controlling disease and prolonging survival in patients with advanced pancreatic cancer. Despite recent successful phase 3 studies in the first-line setting, there is no defined second-line treatment for patients who experience disease progression following first-line therapy. Consensus guidelines (such as the National Comprehensive Cancer Network (NCCN) guidelines) recommend clinical trial participation in this setting.
The investigators' pre-clinical data suggests that decitabine treatment in the KPC model of pancreatic cancer leads to a significant up-regulation of interferon-related genes and a polarization of the infiltrating immune cells. Based on these results, the investigators have evaluated the effect of single agent decitabine or anti-PD1H (a homologue of PD1 with very similar function and expression pattern) compared to combination therapy (treatment with decitabine followed by PD1H blockade). The investigators' preliminary results showed minimal effect of either agent alone on tumor growth but marked decrease in tumor progression in the combination arm. These results form the foundation of this phase II study.
This study will treat patients with the combination of azacitidine and pembrolizumab. A direct comparison between azacitidine and decitabine in terms of efficacy within a controlled clinical trial has not been performed thus far. In randomized myelodysplastic syndrome (MDS) trials, the remission rates were similar for azacitidine and decitabine but the overall survival in the experimental arm was significantly shorter in the decitabine trial compared to the azacitidine trial. A primary reason to utilize azacitidine in this setting is our desire to amply reduced dose therapy with the goal of maintaining subjects on therapy Low-dose azacitidine is being tested in phase I/II clinical trials for advanced solid tumors-mainly colorectal cancer, small-cell lung carcinomas, ovarian cancer, and breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab | Experimental | Drug: Pembrolizumab, Drug: AzacitidinePatients with advanced pancreatic cancer will receive pembrolizumab with the hypomethylating agent azacitidine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (2 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabAlso: KeytrudaPembrolizumab 200 mg IV every 3 weeks until progression | Drug | Pembrolizumab |
| AzacitidineAlso: Vidaza50 mg/m2 subcutaneous daily for 5 days every 28 days | Drug | Pembrolizumab |
Primary outcome
Progression-Free Survival (PFS)
Time frame: 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.
3 secondary outcomes
Objective Response Rate (ORR)
Time frame: Throughout study duration, up to approx 80 months
Duration of Response (DOR)
Time frame: Throughout study duration, up to approx 80 months
Disease Control Rate (DCR)
Time frame: Throughout study duration, up to approx 80 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41844546Safyan 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 9;31(4):oyag091. doi: 10.1093/oncolo/oyag091.
- Derived from this study: PubMed 39863139Tost 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susan E Bates, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab and Azacitidine in people with Pancreas Cancer, run by Susan E. Bates at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03264404, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2026.