FDA Approves Pafolacianine Sodium Injection for Ovarian Cancer Identification

The FDA has approved pafolacianine sodium injection (Cytalux) for adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions.

The FDA has approved pafolacianine sodium injection (Cytalux) for adult patients with ovarian cancer as an adjunct for intraoperative identification of malignant lesions.1

The approval was based on findings from a phase 3 trial, which showed that pafolacianine sodium injection identified additional lesions that would have otherwise been left behind in 27% of patients with ovarian cancer (n = 134; 95% CI, 0.196-0.352).

Pafolacianine sodium injection is said to be the first targeted fluorescent imaging agent that illuminates ovarian cancer intraoperatively, providing the ability to detect more cancer for surgical removal. The imaging agent is administered as standard intravenous injection over a 1-hour period, before binding to folate receptors that are overexpressed in most epithelial ovarian cancers and illuminates intraoperatively under near-infrared light.

"This FDA approval is a significant milestone towards achieving On Target's mission to make cancer visible during surgery so it can be removed more completely,"  Chris Barys, president and chief executive officer of On Target Laboratories, said in a press release. "We are excited about the potential impact Cytalux can have for patients in their fight against ovarian cancer. Our goal is to make Cytalux a standard of care for ovarian cancer surgery and we look forward to exploring the use of our technology for patients suffering from other cancers."

The use of this injection in ovarian cancer surgery could help to provide greater certainty of complete disease resection, as approximately 97% of patients with ovarian cancer express clear alpha-folate receptor proteins.2

The use of pafolacianine sodium injection in ovarian cancer was investigated in phase 2 (NCT02317705) and phase 3 (NCT03180307) trials and was under Special Protocol Agreement from the FDA. Additionally, the agent has received both fast track and orphan designations from the regulatory agency.

"Complete removal of all malignant tissue is the goal of ovarian cancer surgery, however identifying all lesions can be challenging," said Dr. Janos L. Tanyi, MD, PhD, Associate Professor of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine and Investigator on the Phase 2 and 3 studies. "In the phase 3 study, additional cancer was detected in 27% of patients, showing great promise in the ability of Cytalux to help surgeons identify malignant lesions that may otherwise be missed during surgery."

The phase 2 study enrolled 29 patients who were 18 years of age or older with a primary diagnosis, or high clinical suspicion, of ovarian cancer. Participants received pafolacianine sodium injection prior to planned debulking surgery.3

Results showed that when controlling for correlation of detection among multiple lesions within a single patient, pafolacianine sodium injection had a sensitivity of 97.97% (95% lower boundary CI = 87.75) and a positive predictive value of 94.93% (95% lower boundary CI = 86.13). Additionally, 48.3% (n = 14/29; 95% CI, 0.29–0.67) of patients had at least 1 additional lesion detected by pafolacianine sodium injection.4

In terms of safety, 8 patients experienced mild drug-related adverse effects (AEs). The most common AEs reported included infusion reaction, nausea, vomiting, and abdominal pain.

Data from the phase 2 trial led to the ongoing phase 3 trial.5 Additionally, data from a subgroup analysis of the phase 3 trial showed that in patients who underwent interval debulking surgery, the identification rate of additional lesions was 40% (n = 48; 95% CI, 0.270-0.534). However, On Target Laboratories stated that this subgroup analysis utilized a smaller analysis set than the primary end point and was not adjusted to control for error. Therefore, the results may be overstated and should be cautiously interpreted.

The patient-level false positive rate of pafolacianine sodium injection with near-infrared fluorescent light with respect to the detection of ovarian cancer lesions confirmed by central pathology was 20.2% (95% CI, 13.7%-28.0%).

Additionally, pafolacianine sodium injection is currently being investigated in the phase 3 ELUCIDATE trial (NCT04241315) for use in the intraoperative detection of lung cancer lesions. This multicenter trial will evaluate the safety, efficacy, and tolerability of pafolacianine sodium in patients with lung cancer and is expected to enroll up to 130 patients. The first patient was enrolled in the study in July 2020, and preliminary data is expected in 2021.6


  1. On Target Laboratories Announces FDA Approval of Cytalux (pafolacianine) injection for identification of ovarian cancer during surgery. News release. On Target Laboratories, Inc. November 29, 2021. Accessed November 19, 2021. https://prn.to/3FVzoIS
  2. Markert S, Lassmann S, Gabriel B, et al. Alpha-folate receptor expression in epithelial ovarian carcinoma and non-neoplastic ovarian tissue. Anticancer Res. 2008;28(supp 6A): 3567-3572
  3. Phase 2 study of OTL38 for intra-operative imaging of folate receptor-alpha positive ovarian cancer. ClinicalTrials.gov. Updated September 9, 2019. Accessed March 3, 2021. https://clinicaltrials.gov/ct2/show/NCT02317705
  4. Randall L, Wenham R, Low P, et al. A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer. Gynecologic Oncology. 2019;155(supp 1):63-68. doi:10.1016/j.ygyno.2019.07.010
  5. OTL38 for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer. ClinicalTrials.gov. Updated December 8, 2020. Accessed February 3, 2021. https://clinicaltrials.gov/ct2/show/NCT03180307
  6. First patient enrolled in the phase 3 ELUCIDATE trial of pafolacianine sodium (formerly OTL38) in the intraoperative identification of lung cancer lesions. News release. On Target Laboratories, Inc. July 8, 2020. Accessed March 3, 2021. https://prn.to/386WSMH