Detection of peritoneal metastases during cytoreductive surgery using pegsitacianine, a pH sensitive imaging agent: Final results from a phase 2 study.
Authors: Wagner Patrick , Levine Edward Allen , Kim Alex , Shen Perry , Fleming Nicole D. , Westin Shannon Neville , Berry Laurel K , Karakousis Giorgos Constantine , Tanyi Janos Laszlo , Olson Madeline , Ostrander Brian , Krishnan Kartik , Bartlett David L. 
Published: June 2023

3003

Background: For patients with peritoneal metastatic disease, extent of cytoreductive surgery (CRS) is a major prognostic factor for long-term survival, regardless of primary tumor type. Pegsitacianine is a systemically delivered pH-sensitive polymeric micellar fluorescent nanoprobe developed to intraoperatively identify residual disease and augment the completeness of CRS following standard of care radiographic imaging, visualization, palpation, and intended resection. Methods: NCT04950166 was a Phase 2, non-randomized, open-label, multi-center U.S. study. Patients eligible for CRS were administered a single intravenous dose of pegsitacianine at 1 mg/kg within 24-72 hours prior to surgery. After completion of intended CRS, the peritoneal cavity was systematically re-examined under near-infrared (NIR) illumination to evaluate for fluorescent tissue. Post-standard of care fluorescent tissue detected by pegsitacianine guidance was excised and sent for evaluation for presence of residual tumor by histopathology. Clinically significant events (CSE) were defined as detection of histologically confirmed residual disease excised under pegsitacianine guidance following standard CRS, resulting in additional excision or a change in the assessment of completeness of CRS. Treatment-related and treatment-emergent adverse events were coded by CTCAE (v5.01). Results: A total of 40 patients were enrolled and evaluable for CSE. Evaluable patients were defined as patients who completed pegsitacianine dosing, underwent CRS with post-SOC evaluation of the peritoneal cavity, and had evidence of disease upon histopathological evaluation of surgical specimens. These 40 patients represented 6 different primary tumor types (appendiceal, colorectal, endometrial, mesothelioma, ovarian, pancreatic). At the patient level, CSEs were detected in 20 of 40 (50%) patients. Patient-level false positive rate – wherein all pegsitacianine-guided fluorescent tissue specimens resected post-CRS were determined to be negative for cancer by histopathology – occurred in 12.5% of patients. Pegsitacianine was well tolerated with no SAEs. Treatment-related, non-anaphylactic infusion reactions occurred in 26% of patients and were transient, with a median duration of 9 minutes. Conclusions: Pegsitacianine received Breakthrough Therapy Designation from the U.S. Food and Drug Administration as a result of data collected in this trial. Pegsitacianine is well-tolerated and facilitates the recognition of occult residual disease following CRS. The high rate of residual disease detection suggests pegsitacianine has the potential to augment surgeon performance during CRS, leading to improved completeness of cytoreduction and patient outcomes. Clinical trial information: NCT04950166 .