Combo of 177Lu-PSMA-617 and novel radiosensitizer effective in mCRPC

Combination treatment with the investigational radiosensitizer idronoxil (NOX66) and the FDA-approved targeted radioligand therapy ¹⁷⁷Lu-PSMA-617 (Lu 177 vipivotide tetraxetan; Pluvicto) showed promising safety and efficacy in patients with heavily pre-treated metastatic castration-resistant prostate cancer (mCRPC).

Findings from a phase 1/2 trial published in The Journal of Nuclear Medicine showed that the novel radionuclide combination induced a ≥50% PSA decline in more than 60% of the patients treated. The median overall (OS) survival was 19.7 months.^1,2

“NOX66 has shown potential as a radiation sensitizer in prostate cancer. Our study was developed to determine if combining NOX66 with ¹⁷⁷Lu-PSMA-617 could improve treatment response with minimal increase in toxicity for mCRPC patients,” study investigator Louise Emmett, MD, MBChB, FRACP, director of Theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney, Australia, stated in a news release.

Overall, the published results included data for 56 men with progressive mCRPC who had previously received chemotherapy and novel androgen signaling inhibitors (ASI). The treatment regimen consisted of up to 6 doses of ¹⁷⁷Lu-PSMA-617 administered in combination with varying doses of idronoxil.

The median patient follow-up was 21.8 months. Across the population 86% of patients experienced at least some decline in their PSA level. Additionally, 34 (61%) patients had a PSA decline ≥50%. The median PSA progression-free survival was 7.5 months.

The investigators also found that baseline PSMA tumor volume was the strongest indicator of response to treatment and OS; higher tumor volume was linked to worse response; and prior ASI treatment >12 months was linked to better OS.

In the news release, Emmett explained her interpretation of these outcomes: “First, we need to ensure that men receive treatment earlier, before they have high-volume disease, and second, we need to explore why men with high-volume disease respond to treatment poorly.” She added, “Do we need to personalize radionuclide dose based on disease volume to get better treatment responses in men with high-volume disease? Further research is needed. It is clear, however, that trials like this help us explore how to safely prolong treatment responses and help men live longer, better lives.”

¹⁷⁷Lu-PSMA-617 was approved in March 2022 for the treatment of patients with PSMA-positive mCRPC in the post androgen receptor pathway inhibition, post taxane-based chemotherapy setting.³ The approval was based on findings from the phase 3 VISION trial, in which 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.⁴

References

1. New Radionuclide Combination Therapy Safe and Effective in Metastatic Prostate Cancer Patients. Published online April 17, 2022. Accessed April 14, 2022. https://bit.ly/38QQc8L

2. Pathmanandavel S, Crumbaker M, Yam AO, et al. _¹⁷⁷Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial. J Nucl Med. 2022;63(4):560-566. doi: 10.2967/jnumed.121.262552.

3. 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

4. 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).