Phase 2 trial launches of (177Lu) rhPSMA-10.1 injection in mCRPC

The first patients have been enrolled in a phase 2 trial (NCT05413850) evaluating the safety and anti-tumor activity of (177Lu) rhPSMA-10.1 injection for metastatic castration-resistant prostate cancer (mCRPC).¹

Final results from the phase 1 portion of the study showed encouraging radiation dosimetry results.

"This is an important step forward in the development of Lutetium (177Lu) rhPSMA-10.1 injection and builds on the strong data seen in the phase 1 clinical trial,” said David Gauden, DPhil, CEO of Blue Earth Therapeutics, in a news release.¹ “Commencement of treatment of patients at full intended therapeutic dosing levels provides a great opportunity to assess the benefit this therapy can bring to patients. With up to 20 sites enrolling patients, we expect to see first results from the study early next year. We are grateful to the physicians and patients of Biogenix Molecular in Florida, who have just recruited the first patients for the study."

In total, the study plans to enroll 82 patients across both the phase 1 and phase 2 portions of the study. Participants will be enrolled through clinical trial sites across the US and the Netherlands.² The phase 2 study will enroll patients who have progressed following at least 1 novel androgen axis drug but have not received prior taxane-based chemotherapy.

To be eligible for enrollment, patients need to have a serum testosterone level less than 50 ng/dL, an ECOG performance score of 0 to 2, a life expectancy of at least 6 months, and adequate bone marrow reserve and organ function, among other criteria.

According to Blue Earth Therapeutics, the design of the study is in line with the FDA’s Project Optimus initiative, where the goal is to front-load radioactivity in earlier treatment cycles.

The company noted, “The study is testing multiple dosing regimens that focus on delivering higher radiation doses when tumor burden is usually highest, at the beginning of treatment. This approach contrasts to pivotal studies of earlier radioligand therapies where the same dose was administered in every cycle regardless of tumor burden.”

Patients in the study will either receive a higher loading dose in the first 2 treatment cycles or have a shorter time between the administration of the first 3 doses, moving from 3 weeks rather than the usual 6 weeks.

The primary outcome measure is the number of patients with an antitumor response, defined as at least a 50% reduction in prostate-specific antigen level from baseline. The study is also assessing radiographic progression-free survival and safety.

According to Blue Earth, initial study results may be available as soon as the first half of 2026.

Phase 1 data on (177Lu) rhPSMA-10.1 injection

Final results from the phase 1 portion of the study showed encouraging radiation dosimetry results with lutetium (177Lu)-rhPSMA-10.1 injection in patients with mCRPC.³

In the trial, radiation dosimetry was performed for up to 3 cycles of treatment with 177Lu-rhPSMA-10.1 injection. The study included 13 patients with mCRPC. Overall, the results demonstrated a favorable ratio between radiation doses absorbed in the tumor vs the dose delivered to key healthy organs, such as the kidneys and salivary glands.

Specifically, the mean tumor-to-kidney ratio was 32, and the mean tumor-to-salivary gland ratio was 73. The median absorbed radiation dose to tumors was 8.9 Gy for each GBq administered radioactivity, compared with a mean absorbed radiation dose of 0.27 Gy/GBq in the kidneys and 0.13 Gy/GBq in the salivary glands.

Additionally, the mean biological half-life in tumors was 338 hours. According to the company, “When paired with the 6.7-day physical half-life of 177Lu, this gives an effective mean half-life of 91.4 hours. This allows delivery of radiation to tumors over many days: one and a half to twice the reported data for established agents in this class.”

REFERENCES

1. Blue Earth Therapeutics initiates phase 2 clinical trial evaluating the efficacy and safety of Lutetium (177Lu) rhPSMA-10.1 Injection in metastatic castrate resistant prostate cancer. News release. Blue Earth Therapeutics Ltd. May 1, 2025. Accessed May 6, 2025. https://www.prnewswire.com/news-releases/blue-earth-therapeutics-initiates-phase-2-clinical-trial-evaluating-the-efficacy-and-safety-of-lutetium-177lu-rhpsma-10-1-injection-in-metastatic-castrate-resistant-prostate-cancer-302441668.html

2. Anti-tumour activity of (177Lu) rhPSMA-10.1 injection. ClinicalTrials.gov. Last updated March 20, 2025. Accessed May 6, 2025. https://clinicaltrials.gov/study/NCT05413850

3.Blue Earth Therapeutics reports key results from Lutetium (177Lu) rhPSMA-10.1 injection phase 1 clinical trial. News release. Blue Earth Therapeutics Ltd. March 13, 2025. Accessed May 6, 2025. https://www.prnewswire.com/news-releases/blue-earth-therapeutics-reports-key-results-from-lutetium-177lu-rhpsma-10-1-injection-phase-1-clinical-trial-302400601.html