Pafolacianine to Detect Folate Receptor-Positive Ovarian Cancer

Janos Tanyi, MD, University of Pennsylvania, Philadelphia, PA, shares results and insights from the phase 3 to confirm the safety and efficacy of pafolacianine for the detection of folate receptor-positive ovarian cancer.

In a phase 3 study, an extra tumor lesion on tissue, which was not planned for removal, was identified in 33% of patients, after the use of pafolacianine.

Transcript:

My name is Janos Tanyi. I'm an associate professor of the Department of Obstetrics and Gynecology, and the Division of Gynecologic Oncology at the University of Pennsylvania.

What is the current treatment landscape for ovarian cancer?

The primary treatment of ovarian cancer is the combination of surgery and chemotherapy. It can be started with the surgery as primary debulking followed by adjuvant chemotherapy or can be a neoadjuvant chemotherapy followed by interval debulking surgery and then more adjuvant chemotherapy. The surgery and the chemotherapy work together to decrease the amount of disease. Therefore, the surgery is called debulking — we try to remove the bulk of the disease, remove as much disease as possible. Of course, the optimal would be an R0, no gross residue left behind. We know from the literature that when no gross residue is left behind, the patient's prognosis and survival benefit are the best.

What is pafolacianine?

Pafolacianine sodium, or other name is OTL-38, is an antibody and an imaging agent conjugate. It is a folate acid analogue, conjugated together with an indocyanine green-like fluorescent agent. This antibody and fluorescent agent conjugate get injected into the patient's body and circulate in the blood and then stick on the surface of the particle cells that overexpress folate receptor alpha. Folate receptor alpha is overexpressed in many solid tumors, including high-grade serious ovarian carcinomas. Some publications presented that, in high-grade serious ovarian carcinomas, 97% of those overexpress on a moderate or high level folate receptor alpha. This particular agent sticks on the surface and by endocytosis, accumulates inside of their ovarian cancer cells and stays for up to 24 hours. This makes it very possible and easy to see these tumor nodules during the surgery, using a special camera system.

What previous research done on pafolacianine led to this study?

This study is a phase 3 study, but we had a phase 1 and a phase 2 study before. In the phase 1 study, we were able to identify the optimal dose range and timing of a pafolacianine sodium injection in 30 healthy volunteers. And thereafter we proved the concept that the OTL-38 stuck on the surface of the ovarian cancer cells and accumulated in the ovarian cancer cells. And then, those particle tumor nodules were able to be identified using a near-infrared imaging system during the surgery on 12 ovarian cancer patients. In the phase 2 study, on 225 lesions removed from 29 ovarian cancer patients, we were able to determine the sensitivity of that agent, which was 98% in that particular study. Also, in this phase 2 study, we found that in 49% of the patients we were able to identify 1 or more additional lesions during the surgery. We were able to identify these only using the OTL-38 combined with near-infrared intraoperative real-time imaging, we did not recognize those lesions with normal white light observation or manual palpation.

What were the findings of this phase 3 study?

In the phase 3 study, the primary objective was to evaluate the efficacy of OTL-38: What percentage of the patients can identify 1 or more additional lesions with OTL-38 combined with intraoperative molecular imaging on tissue, which was not planned for removal? What did we not identify with a normal white light observation or manual palpation? And the primary objective was 33%, meaning that in 33% of the patients we were able to identify extra tumor lesion on tissue, which was not planned for removal.

In this study, we found that the false positive rate was 32%, which sounds high. But removing false positive lesions, which is fluorescence but does not contain tumor, we found that  did not worsen the surgical risk of those patients.

Also, I would like to share that this particular agent is not toxic, which means that the adverse event profile is very mild. The most frequently seen adverse events were nausea, vomiting, abdominal pain, headache. 97% of these adverse events were mild or moderate, and all of them resolved within 24 hours without any treatment.

What are the potential real-world applications of these findings?

These particular fluorescents, 2 more specific agents combined with intraoperative real-time near-infrared imaging, is an adjunct for the surgeon to reach a more complete debulking. We did a questionnaire asking the surgeons what their opinion of the intraoperative molecular imaging and 56% of the surgeon said that they changed their surgical plan when using this methodology, and 50% said that they could reach more complete debulking. 62% said that they reached R0, no gross residue left behind.

What are the plans for furthering this research?

Folate receptor alpha, as I mentioned, is overexpressed in many solid malignancies. Here at the University of Pennsylvania, we just finished a phase 3 trial in lung cancer, the results of which will be out soon. Folate receptor alpha is also overexpressed in colorectal cancer, endometrial cancer, and multiple other solid tumors. The application of this particle tumor-specific agent can be applied to more types, which means thousands more patients could benefit from this agent.