A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006)

Abstract

Purpose: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer.

Methods: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light.

Results: From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor-positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported.

Conclusion: This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

Trial registration: ClinicalTrials.gov NCT03180307.

FIG 1.

Study design for phase III trial of pafolacianine injection (0.025 mg/kg) with near-infrared fluorescence imaging in patients undergoing surgery for ovarian cancer.

FIG 2.

Folate receptor alpha levels in malignant epithelial tumors. Slides were digitized using an Aperio slide scanner and images were acquired at 5× and 20×. (A) Normal kidney tissue served as the positive control. (B) Normal kidney tissue incubated with an isotype-matched nontargeting primary antibody served as the negative staining control. Representative folate receptor alpha expression in malignant epithelial tumors was depicted by H-scores where an intensity score of (C) 1 was considered weak, (D) 2 moderate, and (E) 3 strong, and a cellularity of 1 was < 33%, 2 was 34% to 65%, and 3 was > 66%.

FIG 3.

CONSORT diagram depicting enrollment and random assignment of patients within the trial, as well as reasons for removal of patients from the trial. FR, folate receptor; PS, pafolacianine.

FIG 4.

Visualization of ovarian cancer lesions in the right paracolic gutter using (A) normal white light compared with (B) NIR fluorescence imaging following pafolacianine injection. NIR, near-infrared imaging.