Detection of Residual Peritoneal Metastases Following Cytoreductive Surgery Using pegsitacianine, a pH Sensitive Imaging Agent
Introduction
The ON-BOARD platform of pH-sensitive polymeric micelles is being developed by OncoNano Medicine as a technology to deliver cancer interventions to tumors specifically, while minimizing systemic exposure and toxicity. Pegsitacianine is a formulation of the ON-BOARD micelle technology to which has been conjugated a fluorophore, indocyanine green. Pegsitacianine, therefore, is a systemically-delivered 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. For patients with peritoneal metastatic disease, completeness of cytoreductive surgery (CRS) is a major prognostic factor of long-term survival, regardless of primary tumor type.
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 pathologically-confirmed residual disease excised under pegsitacianine guidance following standard 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 – completed pegsitacianine dosing, underwent CRS with post-SOC evaluation of the peritoneal cavity, and had histopathology 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 specimens resected post-CRS were determined to be negative for cancer by histopathology – occurred in 20% of patients. Pegsitacianine was well tolerated with no SAEs. Treatment-related, non-anaphylactic infusion reactions occurred in 25% of patients and were transient, with a median duration of 9 minutes.
Conclusion
Pegsitacianine was well-tolerated and facilitated 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. This robust data set earned pegsitacianine a Breakthrough Therapy designation from the FDA. A pivotal trial to support the registration of pegsitacianine with the FDA is currently being planned.