Recruiting
Phase 2

Combination Therapy

Sponsor:

Gulam Manji

Code:

NCT06048484

Conditions

Pancreatic Ductal Adenocarcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Stereotactic body radiotherapy (SBRT)

Zimberelimab

Quemliclustat

Etrumadenant

Modified FOLFIRINOX

Study Details

Brief 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). 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.

Conditions

Pancreatic Ductal Adenocarcinoma

Study ID

NCT06048484

Start date

May 10, 2024

Status verified date

Feb, 2026

Completion date

Apr, 2027

Anticipated

Primary completion date

Apr, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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.
  • 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:

Exclusion Criteria:

  • 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).
  • 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.

Study Design

Enrollment

60 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: Safety run-in

Prior 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)

active comparator: Arm B: SBRT with Zimberelimab (AB122) Alone (Control Arm)

Prior 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)

experimental: Arm C: SBRT, Zimberelimab with quemliclustat (AB680)

Prior 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)

experimental: Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928)

Prior 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)

Interventions

Stereotactic body radiotherapy (SBRT)

SBRT 40 gray (Gy) over 5 fractions

Zimberelimab

240 mg intravenously (IV)

Quemliclustat

100 mg IV

Etrumadenant

150 mg orally

Modified FOLFIRINOX

  • 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)

Primary outcome measure

  • Change in the number of intratumoral CD8+ T-cells [ Time Frame: Perioperative ]

Central Contacts and Locations

Central contacts

Research Nurse Navigator

212-342-5162cancerclinicaltrials@cumc.columbia.edu

Locations

Northwell Health R.J. Zuckerberg Cancer Center

Recruiting

Lake Success, New York, United States, 11042

Contacts

dking14@northwell.edu

Principal Investigator:

Daniel King, MD., PhD.

Columbia University Irving Medical Center

Recruiting

New York, New York, United States, 10032

Contacts

Research Nurse Navigator

212-342-5162cancerclinicaltrials@cumc.columbia.edu

Principal Investigator:

Gulam Manji, MD, PhD

UNC Hospitals, The University of North Carolina at Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27514

Contacts

Ashwin Somasundaram, MD

919-843-7709

University of Pennsylvania, Abramson Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19104

Contacts

Mark O'Hara, MD

215-360-0919Mark.OHara@pennmedicine.upenn.edu

Medical College of Wisconsin

Recruiting

Milwaukee, Wisconsin, United States, 53226

Contacts

Ben George, MD

bgeorge@mcw.edu

More Information

Sponsor

Gulam Manji

Last update posted

Feb 27, 2026

Last verified

Feb, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-22. This information was provided to ClinicalTrials.gov by Gulam Manji on 2026-02-27. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.