Recently, On Target Laboratories announced the publication of results from the Phase 3 006 Study of CYTALUX (pafolacianine) injection for intraoperative imaging of folate receptor positive ovarian cancer that supported its FDA approval in the peer-reviewed Journal of Clinical Oncology.
DocWire News spoke with Janos L. Tanyi, MD, PhD, Associate Professor of Obstetrics and Gynecology in the Perelman School of Medicine at the University of Pennsylvania and Principal Investigator of the study. Dr. Tanyi discussed the challenges associated with treating ovarian cancer, and about the study methodology and findings.
DocWire News: Can you provide us with some background on yourself?
Dr. Janos Tanyi: So my name is Janos Tanyi, and I am an associate professor of the Department of Obstetric and Gynecology in the Division of Gynecological Oncology at the University of Pennsylvania.
What are some of the challenges of treating ovarian cancer?
Most of the ovarian cancer patients when diagnosed is already not one stage, over 70% of those patients in stage three and four, where the disease is all over in the abdomen or even in the chest and ovarian cancer, not just one single tumor lesion, this is hundreds of small tumor lesions or carcinomatosis and lots of fluids. So one of the biggest challenge, how to remove or debug or decrease the amount of the tumor, the tumor burden, and decrease down even to no evidence of disease combining surgery and chemotherapy.
Talk to us about the study you led – what was the methodology, and what were the results?
All right. This study was a phase three study around the safety and efficacy of pafolacianine sodium, another name OTL-38, for intraoperative molecular imaging during cytoreductive surgery of folate receptor alpha positive ovarian cancer. So this is well known that our ability as surgeon to achieve complete cytoreduction, that this is well known that our ability of surgeon to achieve complete cytoreduction impacts on the survival and the prognosis of our patients and survival enhance on those particular patients where we can reach our zero cytoreduction, so no residual disease left behind. To achieve complete cytoreduction, it relies upon the accurate detection and if possible, removal of all tumor lesions and today, surgical oncologist and gynecological oncologist has two instruments to reach this state, the visual inspection during the surgery under the white surgical light and manual palpation to identify and remove all the tumor nodules.
But there are limitation of this approach because we can overlook lesions mostly if they are small in size. So the surgeon requires some help to augment these process and identify lesions and the application of real time fluorescence molecular imaging using tumor specific agents are under development in the United States and many other places in the world to address this particular need.
In our study, we targeted folate receptor alpha, which is overexpressed in many solid tumors. Folate receptor alpha there is couple of publication is overexpressed, 97% of the high grade serious ovarian cancers on a moderate and high level, and by the same publication by market and colleagues. Normal ovary does not express folate receptor alpha, has a very limited folate receptor alpha expression. So OTL-38, our agent is a folic acid analog conjugated with an indocyanine green dye, and this is a perfect tumor specific agent that we can use folate alpha receptor receptor positive cancer surgeries.
In this particular study, our primary objective was to avoid the efficacy, so how many percent of the patients, we are able to identify one or more additional lesion using OTL-38 and near infrared intraoperative in real time imaging, which was not identified with visual observation and manual palpation on tissue, which was not planned for removal. The study was conducted between March of 2018 up to April of 2020. In 11 intensive care cancer centers, 10 in the United States and one in the Netherlands. Altogether 150 patients received the full OTL-38 dose and these 150 patient comprised the safety analysis set. In this particular study, the patient serve as their own control, which means we compare the surgical plan before and after intraoperative molecular imaging. So at the morning of the surgery, the patient received an OTL-38 infusion and in the OR the surgeon after opened abdominal cavity, evaluated and documented all suspicious lesion just with normal white light visual inspection and manual palpation.
And thereafter, an intraoperative molecular imaging happened in the OR and the surgeons again documented all fluorescent lesions all suspicious lesions documented. And this particular time the surgeon had the ability to change the pre-fluorescent surgical plan after the surgery was conducted. And once the surgery was completed, we did another intraoperative molecular imaging to identify all lesions which was overlooked or left behind. All single tumor lesion and tissue samples, which were removed were sent to a center of pathology laboratory in the Moffitt Cancer Center for hematin staining and for fully receptor of immune histo chemistry. So in this particular study, as I mentioned, the primary point was the efficacy. The secondary endpoint was the US as safety further and also the fast positive rate and the sensitivity. This particular study met with the primary endpoint, which were 33%, which means the 33% of our patients, we were able to identify one or more additional tumor lesions.
What we were able to identify with OTL-38 and a near infrared intraoperative imaging and was not identified by visual inspection and manual palpation on tissue, which was originally not planned for removal. It was very interesting that this person is changed by the surgery type interval. Debugging surgery, this percentage increased the 39.7% and in primary debugging surgery it was 17.9%. The secondary endpoint sensitivity in this study was 83% and the phos rate was 32.7%. We performed the post analysis and avoided those surgeries’ outcome who performed more than five intraoperative molecular imaging and we found that the sensitivity increased to almost 87% and phos decreased to 28%. In this particular study.
Amongst those surgeons who were more experienced using this technology, we avoided the first grade by the request of FDA because removing fluorescence, but two more, not containing tissue, can increase the surgical risk. We avoided our patient population compared to the and we found that removing fast positive tissue, which is fluorescence but does not contain cancer, did not worsen the surgical risk in these particular patients. We also evaluated the safety profile of OTL-38 and no new safety signal emerged. The most regularly seen side effect was abdominal pain, nausea, vomiting, occasional headache, which already saw within 24 hours without any medical treatment and 97% of these side effects were mild or moderate.
What are the clinical implications of these findings?
So the clinical implication, we surveyed the investigators in this study and asked their opinion about the intraoperative molecular imaging, and the investigators reported that 56% of them change the process and surgical plan. After intraoperative molecule imaging. 50% of them reported that they did more complete cytoreduction and 62.8% reported that they reached R zero, no gross residual. So R zero complete debugging with this technology during the surgery. So for receptoralpha is overexpressed in many solid tumors. I think this agent is already FDA approved by FDA approved for ovarian cancer. And recently the long phase three study also completed. So we are very eager to see the results, but as many solid tumors express folate receptor alpha, I think the application of pafolacianine sodium combined with intraoperative molecular imaging can be applied for other solid tumor debugging surgeries, identifying further lesions make those surges more complete. So I think this will be much more spread and widespread application within a couple of years on the field.