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Pancreatic Ductal AdenocarcinomaPhase 2AIRPancNCT06048484

Combination Therapy in Patients With Localized Pancreatic Ductal Adenocarcinoma

A Phase 2 study testing Stereotactic body radiotherapy (SBRT), Zimberelimab and Quemliclustat in people with Pancreatic Ductal Adenocarcinoma, run by Gulam Manji at 5 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The purpose of this study is to combine standard radiation therapy with drugs that encourages the body's immune system against cancer cells and simultaneously adding drugs which also target the pathway that the tumor uses to evade the immune system (CD73 and A2a/b). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Pancreatic Ductal Adenocarcinoma
What is being tested?
Stereotactic body radiotherapy (SBRT), Zimberelimab and Quemliclustat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
5 sitesUnited States
Study dates
10 May 2024to Apr 2027
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

  • Histological or pathological confirmation of pancreatic adenocarcinoma Cytologic or histologic proof of pancreatic ductal adenocarcinoma (PDAC) needs to be verified by the treating institution pathologist. A pathological report from non-treating institutions is sufficient to consent and to initiate investigational therapy if tissue sample is unavailable for evaluation at time of consent or enrollment. However, in such a case, PDAC diagnosis should be confirmed by the treating institution pathologist at a later time.
  • Completed 8 cycles of neoadjuvant modified FOLFIRINOX. Omission of oxaliplatin due to adverse events may be allowed in cycles 5-8 with consultation with the principal investigator.
  • Patients with surgically resectable PDAC who are considered appropriate to undergo the applicable operation.
  • Eligible to undergo SBRT.
  • Measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  • No prior surgical, systemic, or radiotherapy for PDAC except for mFOLFIRINOX.
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  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Age ≥ 18 years.
  • Adequate hematological and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to initiation of investigational treatment:

Who cannot join

  • Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including but not limited to anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
  • Patients who are receiving any other investigational agents concurrently.
  • Concomitant treatment with other anti-neoplastic agents (hormonal therapy acceptable).
  • Uncontrolled pleural effusion, pericardial effusion, or ascites.
  • Uncontrolled hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL, or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.
  • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease (Crohn's disease or ulcerative colitis), antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis (some exceptions permissible as outlined per protocol).
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  • History of idiopathic pulmonary fibrosis, interstitial lung disease, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
  • History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Positive HIV test at screening or at any time prior to screening.
  • Active hepatitis B virus (HBV) infection (chronic or acute), defined as having a positive hepatitis B surface antigen (HBsAg) test at screening.
  • --Note: Patients with a past or resolved HBV infection, defined as having a negative HBsAg test and a positive total hepatitis B core antibody test at screening, are eligible for the study.
  • Active hepatitis C virus (HCV) infection, defined as having a positive HCV antibody test followed by a positive HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
  • Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, fatty liver disease, and inherited liver disease.
  • Known active tuberculosis.
  • Inability to swallow medication or malabsorption condition that would alter the absorption of orally administered medications.
  • Pregnant women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents and breastfeeding should be discontinued.
  • History of allergy or hypersensitivity to oxaliplatin, irinotecan, leucovorin, fluorouracil, pegfilgrastim, or any excipients.
  • History of Gilbert's disease or known genotype UGT1A1 *28/*28.
  • Inflammatory disease of the colon or rectum, or severe uncontrolled diarrhea.
  • Active or history of celiac disease.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Trial locations and contacts

5 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Research Nurse Navigator contact

212-342-5162

cancerclinicaltrials@cumc.columbia.edu

5 sites in 1 country

United States5 sites, 5 recruiting

  • UNC Hospitals, The University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina, 27514

    Ashwin Somasundaram, MD, 919-843-7709

    Recruiting

  • Northwell Health R.J. Zuckerberg Cancer Center

    Lake Success, New York, 11042

    dking14@northwell.edu

    Daniel King, MD., PhD.

    Recruiting

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

    Ben George, MD, bgeorge@mcw.edu

    Recruiting

  • Columbia University Irving Medical Center

    New York, New York, 10032

    Research Nurse Navigator, 212-342-5162, cancerclinicaltrials@cumc.columbia.edu

    Gulam Manji, MD, PhD

    Recruiting

  • University of Pennsylvania, Abramson Cancer Center

    Philadelphia, Pennsylvania, 19104

    Mark O'Hara, MD, 215-360-0919, Mark.OHara@pennmedicine.upenn.edu

    Recruiting

Other trials in United States

About this study

Official title: A Phase 2, Open-Label, Multicenter, Randomized Study Evaluating Neoadjuvant Therapy Targeting the Adenosine Immunosuppressive Pathway in Combination With Immune Checkpoint Blockade and Radiation Therapy in Patients With Advanced PANCreatic Ductal Adenocarcinoma Who Are Candidates for Surgical Resection

The purpose of this study is to combine standard radiation therapy with drugs that encourages the body's immune system against cancer cells and simultaneously adding drugs which also target the pathway that the tumor uses to evade the immune system (CD73 and A2a/b). The study hopes that these drugs will work in concert with radiation therapy to kill cancer cells.

The specific goal of this study is to ensure that treatment with zimberelimab and stereotactic body radiation therapy (SBRT) alone or in combination with quemliclustat (a drug which blocks CD73), with or without etrumadenant (a drug which blocks the A2a/b) given before surgery is safe and if it can further increase the immune response against the tumor.

Read the detailed description

The overall objective of this study is to combine standard radiation therapy with drugs that stimulate the body's immune system against cancer cells (by targeting the protein programmed cell death (PD-1), while adding drugs which also target the pathway that the tumor uses to evade the immune system (the CD73 and A2a/b pathways).The main goal of this study is to find out if study treatment with zimberelimab (an antibody which binds the protein PD-1) and stereotactic body radiation therapy (SBRT) alone or in combination with quemliclustat (a drug which blocks CD73), with or without etrumadenant (a drug which blocks the A2a/b) given before surgery is safe and if it can further increase the immune response against the tumor.

The study is divided into two parts (Stage 1 and Stage 2). In Stage 1 participants will undergo 5 days of SBRT and receive zimberelimab, quemliclustat and etrumadenant (Arm A) for 7 weeks before surgery. If this combination is considered safe, the study will proceed to Stage 2. In Stage 2, participants will be randomized into one of three different treatment arms (B - D). All participants will undergo SBRT and will receive either Zimberelimab alone (Arm B), a combination of zimberelimab with quemliclustat (Arm C), or will receive combination of zimberelimab, quemliclustat and etrumadenant (Arm D) for 7 weeks prior to surgery.

Being tested
Stereotactic body radiotherapy (SBRT), Zimberelimab, Quemliclustat, Etrumadenant, Modified FOLFIRINOX

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Stereotactic body radiotherapy (SBRT)Radiation

    SBRT 40 gray (Gy) over 5 fractions

  • ZimberelimabDrug

    Also called AB122

    240 mg intravenously (IV)

  • QuemliclustatDrug

    Also called AB680

    100 mg IV

  • EtrumadenantDrug

    Also called AB928

    150 mg orally

  • Modified FOLFIRINOXDrug

    Also called mFOLFIRINOX

    • Oxaliplatin 85 mg per square meter IV
    • Irinotecan 150 mg per square meter IV
    • Leucovorin 400 mg per square meter IV
    • Fluorouracil 2400 mg per square meter IV
    • Pegfilgrastim injector kit (6mg subcutaneous)
Study groups in NCT06048484
Study groupRoleWhat they receive
Arm A: Safety run-inExperimentalPrior to resection: SBRT 40 Gy over 5 fractions, zimberelimab (AB122) 240 mg intravenously (IV) every 2 weeks for 7 weeks (4 doses), quemliclustat (AB680) 100 mg IV every 2 weeks for 7 weeks (4 doses) and etrumadenant (AB928) 150 mg PO daily for 7 weeks. After resection: mFOLFIRINOX (4 cycles)
Receives: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Zimberelimab; Drug: Quemliclustat; Drug: Etrumadenant; Drug: Modified FOLFIRINOX
Arm B: SBRT with Zimberelimab (AB122) Alone (Control Arm)Active comparatorPrior to resection: SBRT 40 Gy over 5 fractions, 240 mg IV zimberelimab (AB122) every 2 weeks for 7 weeks (4 doses) prior to surgery. After resection: mFOLFIRINOX (4 cycles)
Receives: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Zimberelimab; Drug: Modified FOLFIRINOX
Arm C: SBRT, Zimberelimab with quemliclustat (AB680)ExperimentalPrior to resection: SBRT 40 Gy over 5 fractions, 240 mg IV zimberelimab (AB122) every 2 weeks for 7 weeks (4 doses) prior to surgery in combination with quemliclustat IV at the recommended therapeutic dose (RTD)every 2 weeks for 7 weeks (4 doses) prior to surgery. After resection: mFOLFIRINOX (4 cycles)
Receives: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Zimberelimab; Drug: Quemliclustat; Drug: Modified FOLFIRINOX
Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928)ExperimentalPrior to resection: SBRT 40 Gy over 5 fractions, 240 mg IV zimberelimab (AB122) every 2 weeks for 7 weeks (4 doses) prior to surgery in combination with quemliclustat IV at the RTD every 2 weeks for 7 weeks (4 doses) and etrumadenant (AB928) PO at the RTD daily for 7 weeks prior to surgery. After resection: mFOLFIRINOX (4 cycles)
Receives: Radiation: Stereotactic body radiotherapy (SBRT); Drug: Zimberelimab; Drug: Quemliclustat; Drug: Etrumadenant; Drug: Modified FOLFIRINOX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in the number of intratumoral CD8+ T-cells

    The primary endpoint is change in the number of intratumoral CD8+ T-cells at time of surgery between treatment arm(s) compared to the SBRT + zimberelimab arm (Control Arm B). To obtain CD8+ T-cell count, simple immunohistochemistry (IHC) will be used to quantitate CD8+ T-cells. A designated gastrointestinal (GI) pathologist will review each hematoxylin and eosin (H\&E) stained serial section and IHC slide to oversee the process. Representative areas within the slide will be used for cell counts.

    Measured: Perioperative

Secondary outcomes (6)

  1. Resection rate

    The proportion of patients undergoing surgical resection after randomization. Patients that do not undergo an explorative laparotomy at all or do undergo an explorative laparotomy but not a resection are considered a failure.

    Measured: Week 8

  2. Microscopically Negative Margins (R0) resection rate

    R0 resection rate: Defined as the percentage of eligible patients who underwent surgery with microscopically negative margins (R0). The resection is considered R0 if the inked margin is further than 1 mm distinct from any tumor cells.

    .

    Measured: Week 8

  3. Pathologic Complete Response Rate

    Pathologic complete response rates after R0 or R1 resection as per the Modified Ryan Scheme for Tumor Regression Score (no viable cancer cells). R0 defined as inked margin is further than 1 mm distinct from any tumor cells. R1 defined as macroscopically curative resection, but tumor cells are observed by microscopy at one or more edges of the resected specimen.

    Measured: Week 8

  4. Recurrence free survival

    Defined as investigator assessed survival without overt recurrent pancreatic cancer from the date of randomization. Any sign of recurrent or persistent disease, locoregional or distant, as well as death from any cause is considered an event for this endpoint. Recurrence of disease is defined as radiological evidence of recurrence that is confirmed by biopsy. However, if recurrence is suspected due to participant symptoms consistent with disease recurrence and rising tumor markers (that are not explained due to inflammation or biliary obstruction) may result in sooner scans. All efforts will be made to confirm recurrence by conducting a biopsy if considered safe. If a patient is unable to undergo biopsy to confirm recurrence, these cases will be discussed at the institutional multidisciplinary conference for consensus and discussed with the overall study principal investigator (PI) and the participant will be deemed to have clinical recurrence.

    Measured: 18 months

  5. Overall Survival

    Defined as the period of time between randomization and death from any cause. Participants alive at last follow-up are censored.

    Measured: 4 years

  6. Count of Grade 3 or Higher Adverse Events

    The safety profile will be assessed by the count of grade 3 or higher adverse events as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.

    Measured: 4 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2023
  2. Study start10 May 2024
  3. Primary completionApr 2027 (estimated)
  4. Study completionApr 2027 (estimated)

Resources

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
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06048484
Sponsor's protocol ID
AAAU4206
Acronym
AIRPanc
Status last verified
Feb 2026
First submitted
15 Sep 2023
Last updated
27 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Stereotactic body radiotherapy (SBRT), Zimberelimab and Quemliclustat in people with Pancreatic Ductal Adenocarcinoma, run by Gulam Manji at 5 sites 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 9 inclusion and 21 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: looking for participants now, as of the sponsor's last update on 27 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Research Nurse Navigator (212-342-5162, cancerclinicaltrials@cumc.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the number of intratumoral CD8+ T-cells (time frame: Perioperative). 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 NCT06048484.

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 Feb 2026.

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