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.

Can fluorescence-guided surgery improve optimal surgical treatment for ovarian cancer? A systematic scoping review of clinical studies

“…A literature search of 2817 results yielded 24 clinical studies to be included in our review 16–39. The study inclusion process is illustrated in Figure 2.…”

Updates on fluorescent probes and open‐field imaging methods for fluorescence‐guided cytoreductive surgery for epithelial ovarian cancer: A review

“…The latest phase‐3 trial (NCT03180307) showed that 47 of 109 patients with OC underwent additional resections, for tumours that were detected by the fluorescence signal of OTL38 but were invisible in white light and were undetectable by palpation 62 . Moreover, OTL38 showed a limited safety risk in all trials and steady sensitivity, ranging from 83% to 85%.…”

High-Contrast Detection of Somatostatin Receptor Subtype-2 for Fluorescence-Guided Surgery

“…This approach allows for delineation of tumors from normal tissues in real time to enable safer and more effective removal of cancerous lesions. 1 Increasing evidence suggests that the chemical features of the fluorescent label can strongly influence the in vivo imaging properties of bioconjugates, including their specificity and ability to generate contrast. 2 , 3 Thus, dye selection is critical and has recently emerged as a key technical element of FGS research.…”

“…Fluorescence-guided surgery (FGS) is a method of enhancing intraoperative visualization of tumors, which may be difficult to discern, often through the use of exogenously administered contrast agents that target tumor tissues. This approach allows for delineation of tumors from normal tissues in real time to enable safer and more effective removal of cancerous lesions . Increasing evidence suggests that the chemical features of the fluorescent label can strongly influence the in vivo imaging properties of bioconjugates, including their specificity and ability to generate contrast. , Thus, dye selection is critical and has recently emerged as a key technical element of FGS research. − …”

“…The green fractions were combined and lyophilized to afford FNIR-Tag-DBCO (14.1 mg, 42% yield) as a fluffy green powder. 1 H NMR (500 MHz, MeOD) δ 8.10 (d, J = 14.2 Hz, 2H), 7.88 (dd, J = 9.9, 1.8 Hz, 4H), 7.64 (d, J = 8.0 Hz, 1H), 7.49 (dd, J = 6.3, 2.1 Hz, 1H), 7.40−7.29 (m, 7H), 7.24 (d, J = 9.0 Hz, 1H), 6.35 (d, J = 14.2 Hz, 2H), 5.14 (d, J = 14.2 Hz, 1H), 4.37 (t, J = 5.2 Hz, 4H), 4.14 (t, J = 6.2 Hz, 2H), 3.90 (t, J = 5.1 Hz, 4H), 3.75−3.70 (m, 2H), 3.68 (d, J = 14.0 Hz, 1H), 3.59 (dd, J = 6.0, 3.0 Hz, 5H), 3.52 (dd, J = 5.6, 3.4 Hz, 4H), 3.50−3.38 (m, 11H), 3.29 (s, 6H), 3.26 (two overlapping s, 6H), 2.66 (t, J = 6.3 Hz, 4H), 2.56−2.46 (m, 3H), 2.23 (t, J = 6.9 Hz, 2H), 2.12−2.01 (m, 3H), 1.92 (t, J = 6.0 Hz, 2H), 1.75 (s, 6H), 1.72 (s, 6H) ppm. HRMS (Q-TOF) calculated for C 71 H 93 N 5 O 15 S 2 (M + H) + 1319.6099, observed 1319.6080.…”