Combination Therapy in Patients With Localized Pancreatic Ductal Adenocarcinoma

NCT06048484 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AAAU4206
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (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.

  Perioperative

Secondary Outcomes (6)

• Resection rate

  Week 8

• Microscopically Negative Margins (R0) resection rate

  Week 8

• Pathologic Complete Response Rate

  Week 8

• Recurrence free survival

  18 months

• Overall Survival

  4 years

Study Arms (4)

Arm A: Safety run-in

EXPERIMENTAL

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)

Radiation: Stereotactic body radiotherapy (SBRT); Drug: Zimberelimab; Drug: Quemliclustat; Drug: Etrumadenant; Drug: Modified FOLFIRINOX

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

ACTIVE COMPARATOR

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)

Radiation: Stereotactic body radiotherapy (SBRT); Drug: Zimberelimab; Drug: Modified FOLFIRINOX

Arm C: SBRT, Zimberelimab with quemliclustat (AB680)

EXPERIMENTAL

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)

Radiation: Stereotactic body radiotherapy (SBRT); Drug: Zimberelimab; Drug: Quemliclustat; Drug: Modified FOLFIRINOX

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

EXPERIMENTAL

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)

Radiation: Stereotactic body radiotherapy (SBRT); Drug: Zimberelimab; Drug: Quemliclustat; Drug: Etrumadenant; Drug: Modified FOLFIRINOX

Interventions

Stereotactic body radiotherapy (SBRT) RADIATION

SBRT 40 gray (Gy) over 5 fractions

Arm A: Safety run-in; Arm B: SBRT with Zimberelimab (AB122) Alone (Control Arm); Arm C: SBRT, Zimberelimab with quemliclustat (AB680); Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928)

Zimberelimab DRUG

240 mg intravenously (IV)

Also known as: AB122

Arm A: Safety run-in; Arm B: SBRT with Zimberelimab (AB122) Alone (Control Arm); Arm C: SBRT, Zimberelimab with quemliclustat (AB680); Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928)

Quemliclustat DRUG

100 mg IV

Also known as: AB680

Arm A: Safety run-in; Arm C: SBRT, Zimberelimab with quemliclustat (AB680); Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928)

Etrumadenant DRUG

150 mg orally

Also known as: AB928

Arm A: Safety run-in; Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928)

Modified FOLFIRINOX DRUG

* 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)

Also known as: mFOLFIRINOX

Arm A: Safety run-in; Arm B: SBRT with Zimberelimab (AB122) Alone (Control Arm); Arm C: SBRT, Zimberelimab with quemliclustat (AB680); Arm D: SBRT, Zimberelimab with AB680 and Etrumadenant (AB928)

Eligibility Criteria

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

You may qualify if:

• 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:

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gulam Manji: lead
• Arcus Biosciences, Inc.: collaborator

Study Sites (5)

Northwell Health R.J. Zuckerberg Cancer Center

Lake Success, New York, 11042, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

UNC Hospitals, The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

RECRUITING

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Interventions

Radiosurgery; zimberelimab; quemliclustat

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Gulam Manji, MD, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Research Nurse Navigator

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: September 15, 2023
• First Posted: September 21, 2023
• Study Start: May 10, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (5)