Introduction:

Novel radiohybrid prostate-specific membrane antigen (rhPSMA) radiopharmaceutical, ¹⁷⁷Lu-rhPSMA-10.1, is in development as a potential radioligand therapy agent for patients with metastatic castrate-resistant prostate cancer (mCRPC). Theranostic rhPSMA ligands are unique in that they offer the potential for ¹⁸F diagnostic imaging and subsequently alpha or beta therapy on the same molecule.

This prospective, multicenter, integrated phase 1/2 open-label trial-in-progress will evaluate the safety, efficacy, and radiation dosimetry of ¹⁷⁷Lu-rhPSMA-10.1 in patients with (PSMA positron emission tomography-positive) mCRPC who have experienced disease progression on or after therapy with a novel androgen axis drug (NAAD). The Phase 1 component, which has a dose-escalation design, will determine the recommended treatment dose and regimen for the Phase 2 component, which will then assess the anti-tumor response of ¹⁷⁷Lu-rhPSMA-10.1 using a decrease in prostate-specific antigen (PSA) as a surrogate biomarker endpoint.

Methods:

Phase 1 

Approximately 12 patients with mCRPC that has progressed following therapy with a NAAD and taxane-based chemotherapy (TBC) will be enrolled with the primary objective to assess the dose-limiting toxicities and any treatment-emergent adverse events. Secondary endpoints will evaluate radiation dosimetry and early efficacy measures. Patients will receive 5.55-7.40 GBq ¹⁷⁷Lu-rhPSMA-10.1 per cycle for up to 3 cycles (6-week dosing interval) and will undergo dosimetry assessments using blood and single-photon emission computed tomography/computed tomography at set intervals in the 7d following each cycle.

Phase 2

The primary endpoint, the number of patients with an anti-tumor response (≥50% reduction in PSA from baseline), will be evaluated in ~130 patients. Cohort 1 (prior treatment: NAAD+TBC) will comprise ~60 patients. Cohort 2 (prior treatment: NAAD only) will comprise ~70 patients. Bayesian methods will be used to estimate probability distributions. Secondary endpoints will evaluate survival, radiation dosimetry, safety, and quality of life.

Results:

Conclusion:

Funding: Blue Earth Therapeutics