Initial results published for 177Lu-rhPSMA-10.1 in mCRPC

The radiopharmaceutical ¹⁷⁷Lu-rhPSMA-10.1 showed positive initial efficacy and safety signals in patients with metastatic castration-resistant prostate cancer (mCRPC), according to early data from the independent clinical experience of physicians at the University Hospital Augsburg, Germany, published in the Journal of Nuclear Medicine.^1,2

The efficacy and safety of ¹⁷⁷Lu-rhPSMA-10.1 is currently being explored in an ongoing phase 1/2 trial in the United States (NCT05413850).

Radiographic progression-free survival (rPFS) data showed that among 4 consecutive patients with mCRPC treated with ¹⁷⁷Lu-rhPSMA-10.1, 2 patients had not experienced disease progression at 24 and 18 months of follow-up, respectively. The other 2 patients had a rPFS period of 12 and 15 months, respectively.

All 4 patients had reductions in their PSA levels from the start of treatment, comprising reductions of 100%, 99%, 88%, and 35%. None of the patients experienced a serious treatment-related adverse event.

“Although this experience with ¹⁷⁷Lu-rhPSMA-10.1 represents a small number of patients, we find the results encouraging, with durable radiologic responses for patients with metastatic castrate resistant prostate cancer, including a complete response to therapy sustained beyond two years,” Prof. Dr. med. Constantin Lapa, Department of Nuclear Medicine, University Hospital, Augsburg, Germany, stated in a news release.¹ “This followed our previous dosimetry work with the same patients, which showed that ¹⁷⁷Lu-rhPSMA-10.1 achieved a high Therapeutic Index (TI), delivering a high dose to tumors relative to the absorbed dose to the kidneys, and we look forward to the results of Blue Earth Therapeutics’ ongoing phase 1/2 trial.”

Patients’ ages ranged between 65 and 80 years. Of the 4 patients in the trial, 3 had previously undergone a radical prostatectomy. All patients had an ECOG performance status of 1. Patient PSA levels at baseline were 0.9 ng/mL, 9.9 ng/mL, 15 ng/mL, and 20 ng/mL. Patients were treated with 4 to 6 cycles of ¹⁷⁷Lu-rhPSMA-10.1.²

The efficacy and safety of ¹⁷⁷Lu-rhPSMA-10.1 is currently being explored in an ongoing phase 1/2 trial in the United States (NCT05413850).³ The trial has an estimated enrollment goal of 150 patients with mCRPC. Phase 1 of the trial has primary outcome measures of dose-limiting toxicities and treatment-emergent adverse events and phase 2 has a primary end point of anti-tumor activity, as measured by the rate of patients reaching a ≥50% reduction in PSA level from baseline. The estimated primary completion date for the trial is August 27, 2026.

“We are pleased that these exciting data, from University Hospital Augsburg’s independent experience with ¹⁷⁷Lu-rhPSMA-10.1, have been made available to the physician community,” David Gauden, DPhil, chief executive officer of Blue Earth Therapeutics, stated in a news release.¹ “These promising clinical data give us further optimism in advancing ¹⁷⁷Lu-rhPSMA forward in clinical development, with the hope to help treat patients with metastatic prostate cancer. ¹⁷⁷Lu-rhPSMA-10.1 is based on innovative radiohybrid PSMA theranostic technology, with a carefully optimized pharmacokinetic profile designed to increase retention in cancer deposits while encouraging clearance from normal tissues as rapidly as possible. We then match these properties with long-lived isotopes to maximize the therapeutic index and dose to tumor.”

References

1. Blue Earth Therapeutics Announces Publication of Results from Independent Clinical Experience with 177Lu-rhPSMA-10.1 in Treatment of Metastatic Castrate Resistant Prostate Cancer. Published online and accessed February 20, 2024. https://www.businesswire.com/news/home/20240220362913/en/Blue-Earth-Therapeutics-Announces-Publication-of-Results-from-Independent-Clinical-Experience-with-177Lu-rhPSMA-10.1-in-Treatment-of-Metastatic-Castrate-Resistant-Prostate-Cancer

2. Dierks A, Gäble A, Rinscheid A, et al. First Safety and Efficacy Data with the Radiohybrid 177Lu-rhPSMA-10.1 for the Treatment of Metastatic Prostate Cancer. J Nucl Med. 2024. doi: 10.2967/jnumed.123.266741

3. NIH US National Library of Medicine ClinicalTrials.gov. Anti-tumour Activity of (177Lu) rhPSMA-10.1 Injection. First posted June 10, 2022. Last updated January 22, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05413850