Companies collaborate on FDA-approved PSMA products

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.”

FDA approval of piflufolastat F18

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.

FDA approval of lutetium Lu 177 vipivotide tetraxetan

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).

References

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).