The Food and Drug Administration (FDA) has expanded the approval of Cytalux^® (pafolacianine) to include intraoperative identification of malignant and nonmalignant pulmonary lesions in adults with known or suspected lung cancer, in addition to detecting ovarian cancer lesions.

Cytalux is a fluorescent drug that binds to folate receptor (FR)-expressing cancer cells and illuminates intraoperatively under near infrared light. The expanded approval was based on data from the open-label phase 3 ELUCIDATE study (ClinicalTrials.gov Identifier: NCT04241315), which evaluated the efficacy and safety of pafolacianine in 140 adults scheduled to undergo thoracoscopic or open segmental or subsegmental resection for primary lung lesions that were either confirmed or suspected to be cancer.

“During the Elucidate trial, Cytalux proved to be a valuable surgical tool with its ability to localize lung lesions that may have otherwise been missed,” said Dr Linda Martin, Chief of Thoracic Surgery, University of Virginia School of Medicine. “Cytalux has potential to become standard of care in thoracic surgery because of the safety and efficacy demonstrated in the trial. It is an important tool for surgeons to consider for patients.”

The most common adverse reactions reported with pafolacianine were infusion-related reactions, including nausea, vomiting, abdominal pain, flushing, dyspepsia, chest discomfort, blood pressure elevation, and hypersensitivity. Pafolacianine may cause fetal harm; pregnancy testing prior to administration is recommended.

Cytalux is supplied as a single-dose vial containing 3.2mg/1.6mL (2mg/mL) of pafolacianine.

References

1. On Target Laboratories announces expanded indication of Cytalux^® (pafolacianine) injection for detection of lung cancer during surgery. News release. On Target Laboratories, Inc. Accessed December 16, 2022. https://www.multivu.com/players/English/9123551-on-target-laboratories-expanded-indication-cytalux-injection-lung-cancer-detection-during-surgery/.
2. Cytalux. Package Insert. On Target Laboratories, Inc.; 2021. Accessed December 16, 2021. https://cytalux.com/wp-content/uploads/2022/12/221216_CYTALUX-Prescribing-Information.pdf.

The expanded approval was supported by data from 3 trials that evaluated the effectiveness of Definity in 189 pediatric patients:

• Golding study: 40 patients 1 month to 17 years of age with significant cardiovascular disorders, including heart transplant, Kawasaki disease or congenital cardiovascular anomaly.  
• Fine study: 36 patients 10 to 21 years of age who had previously undergone a heart transplant. 
• Kutty study: 113 patients 5 to 21 years of age with a diagnosis of known congenital or acquired heart disease or suspected cardiac disease.

Findings from these trials showed left ventricular opacification with Definity was successful and provided important information to guide patient management. In Golding, the ability to detect wall motion abnormalities and to perform ejection fraction determinations was improved in the majority of patients (70% and 80%, respectively). 

In the Kutty study, wall motion and/or myocardial perfusion wall motion abnormalities were identified in 11.5% (13/113) of patients. Across all patients, the number of left ventricular segments visualized improved from 13 ± 1 per patient without contrast to 16 ± 1 segments per patient with contrast.

In the Fine study, regional wall motion abnormalities were detected in 8.3% (3/36) of patients, while myocardial perfusion imaging was successful in 89% (32/36). 

With regard to adverse reactions in pediatric patients, no new safety signals were observed in clinical trials.

For pediatric patients, Definity is administered by an intravenous bolus injection only.

Pegulicianine, an optical imaging agent, produces a fluorescent signal after it gets cleaved by cathepsins and matrix metalloproteases. The levels of these enzymes are higher in and around tumor and tumor-associated cells than normal cells. Lumisight is used with the Lumicell Direct Visualization System (DVS) or another fluorescence imaging device approved for use with pegulicianine in the indicated population.

The approval was supported by data from the randomized, intra-patient controlled INSITE trial (ClinicalTrials.gov Identifier: NCT03686215), which included patients with confirmed invasive breast cancer, ductal carcinoma in situ, or both. Study participants were randomly assigned to receive Lumisight by intravenous injection 2 to 6 hours before imaging with the Lumicell DVS or to a control arm; patients in the control arm were not included in the efficacy analysis. 

A total of 357 patients underwent Lumisight-guided imaging following standard of care lumpectomy. When positive fluorescence signal was detected, the tissue was resected with a cavity shave procedure and the region was reimaged. The study assessed the proportion of patients receiving Lumisight who had residual cancer detected and removed after the standard of care lumpectomy. As tissue samples were collected during the standard of care procedure and during the Lumisight-guided procedure, patients in the treatment arm were able to serve as their own control to evaluate outcomes.

Results showed a total of 27 of 357 patients had residual cancer confirmed by histopathology in at least 1 Lumisight-guided shave (7.6%; 95% CI, 5.0-10.8). Findings also showed image-level sensitivity and specificity of Lumisight for residual breast cancer after completion of lumpectomy (calculated from 2346 evaluable images) were 49.1% (95% CI, 36.4-61.9) and 86.5% (95% CI, 84.5-88.3), respectively. A total of 155 patients had at least 1 false positive image and 28 patients had at least 1 false negative image.

The most common adverse reactions reported were hypersensitivity and chromaturia. Anaphylaxis and other serious hypersensitivity reactions were observed with Lumisight administration in clinical studies. 

The prescribing information also includes warnings and precautions regarding the risk of misdiagnosis. False positive and false negative findings may occur during use of Lumisight to detect residual cancer. Additionally, blue dyes used for sentinel lymph node mapping procedures have been shown to interfere with Lumisight imaging and should be avoided before imaging the lumpectomy cavity in patients receiving Lumisight.

“We are immensely proud of the dual approval of Lumisight and Lumicell DVS – we believe this is the first drug-device combination product approved in over a decade to have followed both of the FDA’s most stringent NDA and PMA review processes,” said Howard Hechler, President and Chief Operating Officer, Lumicell. “With the FDA’s approval, LumiSystem is now the first and only imaging combination product capable of detecting cancerous tissue where it matters most, inside the breast cavity.”