Novel Fluorophore May Reduce Complications in Prostate Cancer Surgery

Investigators presented findings from this phase 1 trial (NCT04983862) at the 2024 Society of Surgical Oncology Annual Meeting (SSO).

The use of the investigational fluorophore Illuminare-1 elicited minimal complications in a small cohort of patients with prostate adenocarcinoma who were scheduled to undergo minimally invasive radical prostatectomy, according to findings from a phase 1 study (NCT04983862).¹

At the time of the analysis, 18 evaluable patients had received treatment during the dose escalation phase at doses ranging from 0.25 mg/kg to 1.5 mg/kg. Among 12 of those who received Illuminare-1 at 1.0 mg/kg to 1.5 mg/kg, grade 4 fluorescence for more than 90 minutes during surgery was reported in 8 patients. Additionally, grade 4 fluorescence for 70 minutes was achieved in 1 patient. Investigators also highlighted grade 4 fluorescence lasting for 0, 66, and 87 minutes in 3 patients, respectively.

There was a report of self-limited rash in 1 patient during the study period. Investigators determined that this event was potentially attributable to Illuminare-1.

“This imaging approach could provide a huge benefit to [patients] needing prostate cancer surgery,” study author Timothy F. Donahue, MD, a urologic surgeon at Memorial Sloan Kettering Cancer Center, said in a press release on the use of Illuminare-1 in this population.² “We have urgently needed a better way to see nerves during procedures. We’re very excited about the potential of this technology, not just for prostate cancer surgery but possibly many other operations.”

According to the study authors, a common cause of morbidity during surgery is iatrogenic nerve injury. Sparing the nerves while conducting surgical procedures involves identifying anatomical landmarks, although there are no currently approved intraoperative agents that can assist surgeons visualize the nerves. Investigators aimed to address this gap by organizing a single-arm, open-label, dose-escalation phase 1 study assessing the use of the myelin-binding agent Illuminare-1 in intraoperatively identifying nerves.

As part of the study’s design, investigators will administer Illuminare-1 starting at 0.25 mg/kg before increasing the dose by no more than 0.5 mg/kg at a time until a maximum dose of 2.25 mg/kg is reached, if necessary.³ Additionally, investigators will make use of the Karl Storz D-Light C photodynamic diagnostic as a hardware system.

The trial’s primary end point is determining the safety of Illuminare-1 following intravenous administration while determining the dose level that confers the most clinically useful fluorescence of the obturator nerve, thereby establishing a dose for future studies.

Patients 18 years and older capable of providing informed consent who are scheduled to undergo minimally invasive radical prostatectomy with pelvic lymph node dissection are eligible for enrollment on the trial.

Those with prior pelvic surgery or radiotherapy or known central nervous system or peripheral nervous system disease are ineligible for enrollment. Patients are also unsuitable for study entry if they have significant renal dysfunction or significant hepatic or liver impairment.

Investigators presented findings from this phase 1 trial at the 2024 Society of Surgical Oncology Annual Meeting (SSO).

According to Donahue, future assessments of Illuminare-1 may explore its potential utility in other cancers such as head and neck cancer, gastric cancer, and breast cancer. Investigators may also evaluate the agent in procedures that are not associated with anti-cancer therapy, including hand surgery.

The developers of Illuminare-1, Illuminare Biotechnologies, announced that investigators had completed dosing for the first patient enrolled on the phase 1 trial in January 2023.⁴ Additionally, the FDA granted fast track designation to Illuminare-1 for use as a surgical adjunct in May 2021.⁵

“The fast track designation by the FDA highlights the unmet need for an agent with the potential to reduce unintended iatrogenic nerve injuries across an array of surgical procedures,” Donahue said in a press release at the time of the designation.⁵

References

1. Pere MM, Doudt AD, Durdin TD, et al. PD22-12: A phase-1 trial of real-time intraoperative fluorescent imaging of nerve structures using Illuminare-1, a novel myelin binding fluorophore. J Urol. 2024;211(5S):e466. doi:10.1097/01.JU.0001009504.18450.e0.12
2. Stallard J. New prostate cancer surgery imaging technique could reduce side effects. News release. Memorial Sloan Kettering Cancer Center. May 22, 2024. Accessed May 23, 2024. https://tinyurl.com/429wkdw5
3. Fluorescent imaging of nerves with Illuminare-1 during surgery. ClinicalTrials.gov. Accessed May 23, 2024. https://tinyurl.com/bdh86bdv
4. Illuminare Biotechnologies announces first participant dosed in phase I study of novel nerve visualization investigational fluorophore. News release. Illuminare Biotechnologies, Inc. January 23, 2023. Accessed May 23, 2024. https://tinyurl.com/bdz5j54e
5. Illuminare-1, a novel nerve visualization investigational fluorophore, granted fast track designation by U.S. FDA. News release. Illuminare Biotechnologies, Inc. May 25, 2021. Accessed May 23, 2024. https://tinyurl.com/yc5zuzzw