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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
SBRT 40 gray (Gy) over 5 fractions
240 mg intravenously (IV)
100 mg IV
150 mg orally
* 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)
Northwell Health R.J. Zuckerberg Cancer Center
Lake Success, New York, United States
RECRUITINGColumbia University Irving Medical Center
New York, New York, United States
RECRUITINGUNC Hospitals, The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
RECRUITINGUniversity of Pennsylvania, Abramson Cancer Center
Philadelphia, Pennsylvania, United States
RECRUITINGMedical College of Wisconsin
Milwaukee, Wisconsin, United States
RECRUITINGChange 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.
Time frame: Perioperative
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.
Time frame: Week 8
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. .
Time frame: Week 8
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.
Time frame: Week 8
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.
Time frame: 18 months
Overall Survival
Defined as the period of time between randomization and death from any cause. Participants alive at last follow-up are censored.
Time frame: 4 years
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.
Time frame: 4 months
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.