CPI-008 Snags FDA and EMA Orphan Drug Designation for Imaging in Pancreatic Cancer

The FDA and European Medicines Agency (EMA) have granted orphan drug designation to CPI-008 (cRGD-ZW800-1) for use as an imaging agent for margin detection of pancreatic cancer during surgery.¹

CPI-008 is a novel, integrin-targeted, zwitterionic imaging designed to enhance surgeons’ ability to accurately visualize cancerous cells, thereby optimizing surgical outcomes for patients with pancreatic cancer and select other tumors. The agent has been evaluated in multiple phase 2 clinical trials, with initial focus on its use during the resection of pancreatic, biliary, and head and neck tumors.^1,2 The agent displayed strong imaging capabilities in pancreatic cancer in the phase 2 FLUOPANC study (NCT05518071).^1,3

“Receiving orphan designation from both the FDA and the EMA is a profoundly important milestone for Curadel, granting us valuable incentives to fuel our development efforts,” John V. Frangioni, MD, PhD, founder and chief executive officer of Curadel Pharma, stated in a news release.¹ “As a pioneering company working to introduce significant advances in surgical imaging, the efficiencies of fee exemptions, credits, along with the potential for market exclusivity are vital tools to help us smartly deploy our resources and focus on delivering value to the surgical community.”

How was the FLUOPANC trial designed?

FLUOPANC was a single-center study conducted at Leiden University Medical Center in the Netherlands. ⁴ The study was designed to evaluate the feasibility of CPI-008 across a range of doses.

Investigators enrolled patients at least 18 years of age who were scheduled to undergo open/robotic resection of histologically confirmed pancreatic carcinoma, with or without neoadjuvant therapy. The study excluded patients with a history of clinically significant allergic or anaphylactic reactions; those with renal insufficiency; patients who underwent prior kidney transplant; and patients who were immunocompromised.

The open-label study featured a 2-factorial design, with a goal of enrolling 20 patients with malignant pancreatic or distal/hilar bile duct tumors eligible for surgical resection. The trial featured 4 dose-findings cohorts, along with a fifth expansion cohort. Patients received a single infusion of CPI-008 at 0.05 mg/kg given 2 to 4 hours prior to surgical intervention (cohort 1), at 0.05 mg/kg administered 14 to 24 hours prior to intervention (cohort 2), at 0.025 mg/kg given 2 to 4 hours prior to surgery (cohort 3), or at 0.025 mg/kg administered14 to 24 hours prior to surgery (cohort 4). During surgery, assessments included near-infrared (NIR)–fluorescence of tumor, lymph nodes, possible distant metastasis, and anatomical related structures. Following surgery, NIR-fluorescence of all resected tissue, on gross-macroscopy, bread loafs, and microscopic slides were evaluated.

The study’s primary end point was the visualization of the primary tumor via CPI-008 and NIR-fluorescence imaging, with visualization measured using the tumor-to-background (TBR) ratio both in vivo and ex vivo. A TBR of at least 1.5 was determined to be the cut-off value, since this provided sufficient contrast for adequate visualization and delineation.

Secondary end points included the incidence and severity of adverse effects; the concordance between clinical assessment, histopathological exam, and NIR-fluorescence imaging of the resected tumor, lymph nodes, and/or metastatic lesions and histopathologic results; determining the optimal dose and dose interval of CPI-008; tumor positive margins detected with NIR fluorescence imaging; and the number of tumor-positive lymph nodes and metastases detected by NIR fluorescence imaging.

References

1. FDA and EMA grant orphan drug designation for Curadel’s CPI-008, a targeted zwitterionic imaging drug for pancreatic cancer. News release. Curadel Pharma. January 7, 2026. Accessed January 7, 2026. https://www.curadelpharma.com/2026/01/07/fda-and-ema-grant-orphan-drug-designation-for-curadels-cpi-008-a-targeted-zwitterionic-imaging-drug-for-pancreatic-cancer/
2. Pipeline. Curadel Pharma. Accessed January 7, 2026. https://www.curadelpharma.com/pipeline/
3. Van Dam MA, van Ravens T, Burggraaf J, et al. Optical navigation using tumour-targeted near-infrared (NIR) fluorescence in pancreatic surgery: a phase II feasibility trial of a novel integrin-targeting fluorescent probe cRGD-ZW800-1. Eur J Surg Oncol. 2024;50(suppl 2):108816. doi:10.1016/j.ejso.2024.108816
4. FLUOPANC-trial - fluorescence-guided surgery of pancreatic and bileduct tumors using cRGD-ZW800-1 (FLUOPANC). ClinicalTrials.gov. Updated June 24, 2024. Accessed January 7, 2026. https://clinicaltrials.gov/study/NCT05518071