Phase 1 data show encouraging safety of 177Lu-rhPSMA-10.1 injection in mCRPC

Lutetium (¹⁷⁷Lu) rhPSMA-10.1 injection demonstrated promising radiation dosimetry results in patients with metastatic castration-resistant prostate cancer (mCRPC), according to initial findings from a phase 1 study (NCT05413850).¹

The phase 2 study will enroll approximately 70 patients across 15 clinical trial sites in the United States and Europe.

According to Blue Earth Therapeutics, the developer of the therapy, enrollment of patients in the phase 1 portion of the study was completed in July 2024. Promising findings from phase 1 set the stage for movement into phase 2.

"We are excited by the new data which support our best-in-class thesis and to have a clear path to move from phase 1 to phase 2 in the development of our lead therapy," said Blue Earth CEO, David E. Gauden, DPhil, in a news release from the company.¹ "We remain on track for the opening of phase 2 in the next few months. We also expect to see the full phase 1 results presented at a scientific meeting in 2025.”

In the trial, radiation dosimetry was performed for up to 3 cycles of treatment with ¹⁷⁷Lu-rhPSMA-10.1 injection. Overall, high tumor absorption was observed. According to the company, the results also demonstrated a favorable ratio between radiation doses absorbed in the tumor vs the dose delivered to key normal organs, such as in kidneys and salivary glands. These findings are promising compared with published data on radioligand therapies², the company noted.

Final analysis from the phase 1 portion of the trial remains ongoing. The phase 2 portion of the trial is on track to begin later this year.

According to Blue Earth, phase 2 will explore:

• “Administration of a significantly higher overall injected radioactivity in comparison to recent phase 3 clinical trials of other agents.
• Front loading of administered radioactivity.
• Extending duration of administration of radioactivity to provide longer time on treatment.”¹

The phase 2 study will enroll approximately 70 patients across 15 clinical trial sites in the United States and Europe. Patients enrolled in the study will receive up to 6 cycles of ¹⁷⁷Lu-rhPSMA-10.1 injection at the recommended phase 2 dose level. The primary outcome measure is the number of patients who experience an anti-tumor response, defined as at least a 50% reduction in prostate-specific antigen level.³

Daniel Stevens, head of clinical development and medical at Blue Earth Therapeutics, added in the news release,¹ "The available science increasingly highlights that fixed dosing at fixed intervals is unlikely to be optimal. Front loading radioactivity and extending the time on therapy may lengthen time to disease progression. We will explore these concepts in phase 2. Our intention is to optimize dosing now, with the aim of achieving the best possible outcomes for patients in a future pivotal trial. We think that adapting dosing based on data from the individual patient will be important for improved results."

Additional data on ¹⁷⁷Lu-rhPSMA-10.1

Preclinical data on ¹⁷⁷Lu-rhPSMA-10.1 were presented at the American Association for Cancer Research (AACR) Annual Meeting earlier this year, showing that the combination of ¹⁷⁷Lu-rhPSMA-10.1 and the MEK inhibitor cobimetinib demonstrated an enhanced therapeutic effect vs single agents in preclinical models.⁴

In vivo tumor growth was significantly suppressed with the combination of ¹⁷⁷Lu-rhPSMA-10.1 plus cobimetinib compared with untreated controls (from day 13–30; P < .01) and ¹⁷⁷Lu-rhPSMA-10.1 alone (from day 17–30; P < .001). Survival was also extended in the combination arm, with a median survival of 49 days in the ¹⁷⁷Lu-rhPSMA-10.1 plus cobimetinib arm vs 23 days in the untreated arm (P = .001) and 36 days with ¹⁷⁷Lu-rhPSMA-10.1 alone (P = .002).

According to the authors, these findings support clinical evaluation in men with prostate cancer.

References

1. Blue Earth Therapeutics advances clinical development of lutetium (177Lu) rhPSMA-10.1 injection with promising phase 1 data. News release. Blue Earth Therapeutics Ltd. October 8, 2024. Accessed October 9, 2024. https://www.prnewswire.com/news-releases/blue-earth-therapeutics-advances-clinical-development-of-lutetium-177lu-rhpsma-10-1-injection-with-promising-phase-1-data-302269380.html

2. Ells Z, Grogan TR, Czernin J, Dahlbom M, Calais J. Dosimetry of [177Lu] Lu-PSMA-targeted radiopharmaceutical therapies in patients with prostate cancer: A comprehensive systematic review and meta analysis. J Nucl Med. 2024;65(8):1264-1271. doi:10.2967/jnumed.124.267452

3. Anti-tumour activity of (177Lu) rhPSMA-10.1 injection. ClinicalTrials.gov. Last updated March 4, 2024. Accessed October 9, 2024. https://clinicaltrials.gov/study/NCT05413850

4. Foxton C, Cornelissen B, O’Neill E, et al. Evaluation of a synergistic drug combination with 177Lu-rhPSMA-10.1 for prostate cancer: Results of an in vitro screen and in vivo proof of concept study. Presented at: American Association for Cancer Research Annual Meeting 2024. San Diego, California. April 5-10, 2024. Abstract 694/7. https://www.abstractsonline.com/pp8/#!/20272/presentation/7538