Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent: Final Results from a Phase II Study

Patrick Wagner; Edward A Levine; Alex C Kim; Perry Shen; Nicole D Fleming; Shannon N Westin; Laurel K Berry; Giorgos C Karakousis; Janos L Tanyi; Madeline T Olson; Brian Madajewski; Brian Ostrander; Kartik Krishnan; Charles M Balch; David L Bartlett

doi:10.1245/s10434-024-15165-4

Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using Pegsitacianine, a pH-Sensitive Imaging Agent: Final Results from a Phase II Study

Ann Surg Oncol. 2024 Apr 15. doi: 10.1245/s10434-024-15165-4. Online ahead of print.

Authors

Affiliations

¹ Department of Surgical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA.
² Department of Surgical Oncology, Atrium Health Wake Forest Baptist, Wake Forest University, Winston-Salem, NC, USA.
³ Division of Surgical Oncology, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, OH, USA.
⁴ Department of Gynecologic Oncology and Reproductive Medicine, MD Anderson Cancer Center, Houston, TX, USA.
⁵ Department of Gynecologic Oncology, Atrium Health Wake Forest Baptist, Wake Forest University, Winston-Salem, NC, USA.
⁶ Division of Endocrine and Oncologic Surgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁷ Department of Obstetrics and Gynecology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
⁸ OncoNano Medicine, Inc, Southlake, TX, USA.
⁹ Department of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USA.
¹⁰ Department of Surgical Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, PA, USA. david.bartlett@ahn.org.

PMID: 38622456
DOI: 10.1245/s10434-024-15165-4

Abstract

Background: For patients with peritoneal carcinomatosis, extent of disease and completeness of cytoreductive surgery (CRS) are major prognostic factors for long-term survival. Assessment of these factors could be improved using imaging agents. Pegsitacianine is a pH-sensitive polymeric micelle conjugated to the fluorophore indocyanine green. The micelle disassembles in acidic microenvironments, such as tumors, resulting in localized fluorescence unmasking. We assessed the utility of pegsitacianine in detecting residual disease following CRS.

Patients and methods: NCT04950166 was a phase II, non-randomized, open-label, multicenter US study. Patients eligible for CRS were administered an intravenous dose of pegsitacianine at 1 mg/kg 24-72 h before surgery. Following CRS, the peritoneal cavity was reexamined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Fluorescent tissue identified was excised and evaluated by histopathology. The primary outcome was the rate of clinically significant events (CSE), defined as detection of histologically confirmed residual disease excised with pegsitacianine or a revision in the assessment of completeness of CRS. Secondary outcomes included acceptable safety and pegsitacianine performance.

Results: A total of 53 patients were screened, 50 enrolled, and 40 were evaluable for CSE across six primary tumor types. Residual disease was detected with pegsitacianine in 20 of 40 (50%) patients. Pegsitacianine showed high sensitivity and was well tolerated with no serious adverse events (SAEs). Transient treatment-related, non-anaphylactic infusion reactions occurred in 28% of patients.

Conclusions: Pegsitacianine was well tolerated and facilitated the recognition of occult residual disease following CRS. The high rate of residual disease detected suggests that the use of pegsitacianine augmented surgeon assessment and performance during CRS.

Keywords: Complete resection; Fluorescence; Nanotechnology; Near-infrared; Peritoneal metastasis; Surgical oncology.