Dosing starts in SPOTLIGHT study of rhPSMA-7.3 (18F) PET in biochemically recurrent prostate cancer

July 22, 2020

The phase 3 SPOTLIGHT study is assessing the diagnostic capability of rhPSMA-7.3 (18F) PET in men with suspected prostate cancer recurrence based on elevated PSA following prior therapy.

The first patients have been dosed in the phase 3 SPOTLIGHT trial, which is examining the investigational PSMA-targeted radiohybrid PET imaging agent rhPSMA-7.3 (18F) in men with suspected prostate cancer recurrence.1

The single-arm SPOTLIGHT study (NCT04186845) is specifically assessing the safety and diagnostic capability of rhPSMA-7.3 (18F) PET in men whose elevated PSA following prior therapy has made them clinically suspicious for biochemically recurrent disease. The primary end points of the phase 3 trial are the positive predictive value (PPV) and correct detection rate (CDR) of rhPSMA-7.3 (18F) PET.

"Up to 40% of patients who undergo radical prostatectomy, and up to 50% of patients who undergo radiation therapy will develop local or distant recurrences within 10 years," David M. Schuster, MD, Emory University School of Medicine, who is the coordinating investigator for the SPOTLIGHT study, stated in a press release.

"An important consideration for physicians and their patients is the ability to determine the extent and location of recurrent prostate cancer in order to inform appropriate clinical management for these men. The Phase 3 SPOTLIGHT clinical study is designed to investigate the diagnostic performance of rhPSMA-7.3 (18F) PET imaging as a potential decision-making aid in assessing suspected biochemical recurrence of the disease. At Emory, we scanned our first patient in the SPOTLIGHT study in late June, and we are rapidly recruiting more patients in this exciting trial," added Shuster.

The prospective, multicenter SPOTLIGHT imaging study is aiming to enroll 300 patients in the United States and Europe. The study is using histopathology or confirmatory imaging as a “standard of truth” to assess the primary end points of CDR rhPSMA-7.3 (18F) PET on a patient level and the PPV of rhPSMA-7.3 (18F) PET on a region level. Secondary end points include safety, as well as the inter- and intra-reader agreement of rhPSMA-7.3 (18F) scan interpretations by blinded independent readers.

To enroll on the study, patients must have a history of localized adenocarcinoma treated with curative intent; an elevated PSA indicative of biochemically recurrent disease (PSA greater than 0.2 ng/mL after radical prostatectomy or nadir +2 ng/mL after radiotherapy); and be potentially eligible for salvage therapy with curative intent.2 Patients are not eligible to enroll on SPOTLIGHT if they are currently being treated with androgen deprivation therapy or if they are scheduled to receive an x-ray contrast agent or other PET radiotracer within 24 hours prior to the PET scan.

SPOTLIGHT treatment sites in the United States are located in California, Georgia, Texas, and Virginia. The European treatment location is in Turku, Finland.

Blue Earth Diagnostics (a Bracco company), the developer of rhPSMA-7.3 (18F), previously announced that patient dosing has started in the phase 3 LIGHTHOUSE trial exploring rhPSMA-7.3 (18F) PET in men with newly diagnosed prostate cancer.3 Similar to SPOTLIGHT, LIGHTHOUSE is a multicenter, single-arm imaging study being conducted in the United States and Europe. The primary end points of LIGHTHOUSE are to evaluate the specificity and sensitivity of rhPSMA-7.3 (18F) PET for detecting lymph node metastases as compared with surgical pathology on a patient level.

Some of the data from early clinical experience with rhPSMA-7.3 (18F) PET that led to these two phase 3 trials were shared during the 2020 American Urological Association Virtual Annual Meeting. Findings from a retrospective analysis were presented by the Technical University of Munich (TUM).4 The analysis included 56 patients with intermediate or high-risk prostate cancer. Imaging with rhPSMA-7.3 (18F) PET showed an 81% patient-level sensitivity, an 88% specificity, and an 86% diagnostic accuracy when comparisons were made between on-site image interpretations and histopathological findings.

In the press release announcing the launch of SPOTLIGHT, David Gauden, DPhil, Chief Scientific Officer of Blue Earth Diagnostics, provided some insight on the composition and development of rhPSMA-7.3 (18F).

"The investigational PET agent, rhPSMA-7.3 (18F), is a single isomer product, part of a family of theranostic rhPSMA compounds that Blue Earth Diagnostics exclusively acquired from TUM, via Scintomics Gmbh," said Gauden. "In developing these compounds, we are initially focused on diagnostic PET imaging applications. We selected F18 as the radiolabeling isotope of choice for rhPSMA-7.3 PET based on important attributes, including: a positron energy that enables high resolution PET scans; high yielding chemistry for large batch, centralized manufacturing; and a half-life that enables efficient distribution across broad geographies, to be readily available for patients, independent of select individual hospitals."

References

1. Blue Earth Diagnostics Announces Dosing of Initial Patients in Phase 3 SPOTLIGHT Clinical Trial of Targeted PET Imaging Agent rhPSMA-7.3 (18F) in Biochemically Recurrent Prostate Cancer. https://yhoo.it/3jsmfwz. Posted July 21, 2020. Accessed July 22, 2020.

2. Imaging Study to Investigate Safety and Diagnostic Performance of rhPSMA 7.3 (18F) PET Ligand in Suspected Prostate Cancer Recurrence (SPOTLIGHT). NIH ClinicalTrials.gov. Last updated July 21, 2020. https://bit.ly/2OOjfwu. Accessed July 22, 2020.

3. Blue Earth Diagnostics Announces Dosing of First Patient in Phase 3 LIGHTHOUSE Clinical Trial of Targeted PET Imaging Agent rhPSMA-7.3 (18F) in Newly Diagnosed Prostate Cancer. Posted March 17, 2020. https://bit.ly/2ZMKKg6. Accessed July 22, 2020.

4. BLUE Earth Diagnostics Announces Results From Early Clinical Experience With Targeted Pet Imaging Agent RHPSMA-7.3 (18F) in Men With Intermediate And High-Risk Prostate Cancer. Posted May 18, 2020. https://bit.ly/2ZOm1rB. Accessed July 22, 2020.