CEND-1 in Combination with Neoadjuvant FOLFIRINOX with or Without Panitumumab

Inclusion Criteria:

* Ability of participant OR Legally Authorized Representative (LAR) to understand this study, and participant or LAR willingness to sign a written informed consent
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 - 1
* One or more lesions evaluable on MRI, positive emission tomography (PET)/CT, or dedicated CT scan according to RECIST v1.1
* Patients with histologically confirmed pancreatic ductal adenocarcinomas, colorectal and appendiceal adenocarcinomas
* For cohort 1: Resectable Pancreatic Cancer: No evidence of distant metastasis and tumor mass showing no extension to superior mesenteric artery (SMA) and hepatic artery. There must be clear fat plane between SMA and celiac axis. Patent superior mesenteric vein (SMV/portal vein (PV) with no distortion of venous architecture. Please refer to 2021 NCCN PDAC Guidelines
* For cohort 1: Borderline Resectable Pancreatic Cancer: defined as localized cancer with 1 or more of the following features: "a) an interface between the primary tumor and superior mesenteric vein (SMV)-portal vein (PV) measuring 180o or greater of the circumference of the vein wall, and/or b) short-segment occlusion of the SMV-PV with normal vein above and below the level of obstruction that is amenable to resection and venous reconstruction and/or c) short segment interface of any degree between tumor and hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction and/or d) an interface between the tumor and SMA or celiac trunk measuring less than 180o of the circumference of the artery wall. Please refer to 2021 National Comprehensive Cancer Network (NCCN) Pancreatic Ductal Adenocarcinoma (PDAC) Guidelines
* For cohort 2: Peritoneal Metastases due to Colorectal Cancer or Invasive Adenocarcinoma of the Appendix
* For cohort 3: Oligometastatic colorectal cancer: resectable metastases as determined by multidisciplinary evaluation. Patients with bilobar liver metastases or oligometastatic liver and lung metastases that requires resection of one or more metastases are also allowed
* Eligible for treatment with FOLFIRINOX with or without panitumumab
* Life expectancy of at least 3 months
* Adequate archival tissue from prior biopsy for biomarker evaluation or willingness to undergo biopsy before treatment starts and on treatment
* Medically fit to undergo complex major abdominal surgery at end of study treatment
* Women of childbearing potential must have a negative serum pregnancy test within 72 hours prior to enrollment
* Adequate organ function

Exclusion Criteria:

* Simultaneously enrolled in any therapeutic clinical trial
* Concurrent use of any other anti-cancer therapy, including chemotherapy, targeted therapy, immunotherapy, or biological agents
* Prior chemotherapy or any other investigational agents for the treatment of cancer within 2 years prior to enrollment on this study
* Diagnosed with a psychiatric illness or is in a social situation that would limit compliance with study requirements
* Is pregnant or breastfeeding
* Has a known allergic reaction to any excipient contained in the study drug formulation
* Active Grade 3 (per the NCI CTCAE, Version 5.0) or higher viral, bacterial, or fungal infection within 2 weeks prior to the first dose of study treatment
* New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG
* Known infection with HIV, hepatitis B, or hepatitis C
* Serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator
* Participants with known brain metastases. Screening for brain metastases with head imaging is not required
* History of prior or current synchronous malignancy, except:

  * Malignancy that was treated with curative intent and for which there has been no known active disease for \>3 years prior to enrollment
  * Curatively treated non-melanoma skin cancer, cervical cancer in situ, or prostatic intraepithelial neoplasia, without evidence of prostate cancer