CEND‐1 in Combination with FOLFIRINOX with or without Panitumumab before Surgery for the Treatment of Pancreatic, Colorectal, and Appendiceal Cancers

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
• Males and females age >= 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 1
• One or more lesions evaluable on magnetic resonance imaging (MRI), positron emission tomography (PET)/computed tomography (CT), or dedicated CT scan according to Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1
• Newly diagnosed patients with histologically confirmed pancreatic ductal adenocarcinomas, colorectal and appendiceal adenocarcinomas who have not received previous therapy * NOTE: Patients with colon and appendiceal cancers who have recurrent disease after >= 6 months following post-operative chemotherapy will be eligible
• 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 National Comprehensive Cancer Network [NCCN] pancreatic ductal adenocarcinoma [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) shortsegment 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 NCCN 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
• Absolute neutrophil count >= 1.5 K/UL
• Platelets >= 100 K/UL
• Hemoglobin >= 9 g/dL
• Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR Calculated creatinine clearance ≥ 50 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal by the Cockcroft-Gault equation
• Total bilirubin =< 1.5 x ULN
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]), alanine aminotransferase (ALT) (serum glutamate-pyruvate transaminase [SGPT]) and alkaline phosphatase =< 2.5 times upper limit of normal (if liver metastases are present, then =< 5 x ULN is allowed)
• Women of child-bearing potential and men with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and: * Women - for 9 months after the end of treatment * Men – for 6 months after the end of treatment

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. NOTE: Patients with colon and appendiceal cancers who have recurrent disease after >= 6 months following post-operative chemotherapy will be eligible
• Baseline peripheral neuropathy of grade > 2
• 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 National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [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 electrocardiogram (ECG)
• Known uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C Unless there are clear contraindications, patients with well-controlled HIV, hepatitis B, or hepatitis C infections are not excluded
• 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