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
Gulam Manji
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.
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…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
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…
Interventions
- RadiationStereotactic body radiotherapy (SBRT)
SBRT 40 gray (Gy) over 5 fractions
- DrugZimberelimab
240 mg intravenously (IV)
- DrugQuemliclustat
100 mg IV
- DrugEtrumadenant
150 mg orally
- DrugModified 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)
Locations (5)
- Northwell Health R.J. Zuckerberg Cancer CenterLake Success, New York
- Columbia University Irving Medical CenterNew York, New York
- UNC Hospitals, The University of North Carolina at Chapel HillChapel Hill, North Carolina
- University of Pennsylvania, Abramson Cancer CenterPhiladelphia, Pennsylvania
- Medical College of WisconsinMilwaukee, Wisconsin