Two power players in the PSMA product market, Lantheus and Novartis,have entered into a strategic collaborationregarding their FDA-approved PSMA products.1
Under the agreement, Lantheus’ PSMA-PET imaging agent piflufolastat F18 (Pylarify) will now be used in clinical trials exploring Novartis’ PSMA-targeted therapy lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in patients with prostate cancer.
“The FDA-approval of Novartis’ Pluvicto brings hope to patients and is an exciting advancement in the field of radiopharmaceutical oncology,” Mary Anne Heino, president and CEO of Lantheus, stated in a press release. “We look forward to collaborating to further explore how PSMA-PET imaging agents, like Pylarify, may aid in increasing accessibility to PSMA-targeted therapeutics. As always, our goal is to ‘find, fight, and follow’ serious medical conditions and improve patient outcomes.”
The FDA approved the PSMA-PET imaging agent piflufolastat F18 (also known as 18F-DCFPyL and PyL) in 2021 for identifying suspected metastasis or recurrence of prostate cancer.2 The approval was supported in large part by findings from the phase 3 CONDOR trial, in which 63.9% of men with biochemically recurrent prostate cancer who had no evidence of disease on standard-of-care imaging had a change in intended management after their 18F-DCFPyL–PET/CT scan.3
The multicenter phase study enrolled men with rising PSA after definitive therapy and negative or equivocal standard-of-care imaging. Patients were required to have a PSA level ≥0.2 if they had undergone radical prostatectomy or a PSA level ≥2.0 if they were treated with radiation therapy or cryotherapy.
The primary end point was correct localization rate (CLR), defined as percentage of patients with a 1:1 correspondence between at least 1 lesion identified by PyL–PET/CT and the composite standard of truth (pathology, correlative imaging, or PSA response). PyL scans were read by 3 blinded independent central readers.
Overall, there were 208 evaluable patients, about 85% of whom underwent RP, either alone or with radiation. Median PSA level of the cohort was 0.8 ng/mL, and 68.8% had a PSA level <2.0 ng/mL. Some 27.9% had received at least 1 prior systemic therapy.
Detection of disease as manifested by a positive 18F-DCFPyL–PET/CT scan was 65.9%, 59.6%, and 59.1% by the 3 readers.
The prespecified criterion for CLR success was for the lower limit of the 95% CI to exceed 20% for at least 2 of the 3 readers. For every reader, the lower bound of the 95% CI for the CLR was well in excess of the 20% benchmark, meeting the primary end point of the study.
The CLRs were 85.6% (95% CI, 78.8%-92.3%), 87.0% (95% CI, 80.4%-93.6%), and 84.8% (95% CI, 77.8%-91.9%) by the 3 readers. Some 64% of the evaluable patients had a change in intended management due to the scan.
The FDA approved the targeted radioligand therapy lutetium Lu 177 vipivotide tetraxetan (also known as 177Lu-PSMA-617 and LuPSMA) in 2022 for the treatment of patients with PSMA-positive metastatic castration-resistant prostate cancer (mCRPC) in the post androgen receptor pathway inhibition, post taxane-based chemotherapy setting.4
The approval of LuPSMA was based on findings from the phase 3 VISION trial. In the study, adding LuPSMA to standard of care (SOC) led to a nearly 40% reduction in the risk of death versus SOC alone in patients with progressive PSMA-positive mCRPC.5
The findings, which were presented during the 2021 ASCO Annual Meeting, showed that at a median follow-up of 20.9 months, the addition of LuPSMA improved the median overall survival (OS) by 4 months over SOC alone (HR, 0.62). Adding the targeted radioligand therapy also led to a 5.3-month improvement in median radiographic progression-free survival, translating to a 60% reduction in the risk of progression or death (HR, 0.40).
1. Lantheus Announces Collaboration to Support Prostate Cancer Clinical Development. Published online March 29, 2022. Accessed April 5, 2022. https://yhoo.it/3NS0BRl.
2. Lantheus Receives U.S. FDA Approval of PYLARIFY® (piflufolastat F 18) Injection, the First and Only Commercially Available PSMA PET Imaging Agent for Prostate Cancer. Published online May 27, 2021. Accessed May 27, 2021. https://bwnews.pr/3vtMgBh.
3. Morris MJ, Rowe SP, Gorin MA, et al. Diagnostic performance of 18F-DCFPyL-PET/CT in men with biochemically recurrent prostate cancer: results from the CONDOR phase 3, multicenter study [published online before print February 26, 2021.] doi: 10.1158/1078-0432.CCR-20-4573
4. Novartis Pluvicto™ approved by FDA as first targeted radioligand therapy for treatment of progressive, PSMA positive metastatic castration-resistant prostate cancer. March 23, 2022. https://www.novartis.com/news/media-releases/novartis-pluvictotm-approved-fda-first-targeted-radioligand-therapy-treatment-progressive-psma-positive-metastatic-castration-resistant-prostate-cancer
5. Morris MJ, De Bono JS, Chi KN, et al. Phase 3 study of lutetium-177-PSMA-617 in patients with metastatic castration-resistant prostate cancer (VISION). J Clin Oncol 39, 2021 (suppl 15; abstr LBA4).