A Study of [225Ac]Ac-AKY-2519 in Patients With Metastatic Castration-Resistant Prostate Cancer

BActinium-1: A Phase 1b, Multicenter, Open-label Study to Evaluate the Safety and Efficacy of Intravenous Administration of B7-H3 Radiopharmaceutical ([225Ac]Ac-AKY-2519) in Metastatic Castration-Resistant Prostate Cancer

This is a Phase 1b, multi-center, open-label study to evaluate the safety, tolerability, dosimetry, and pharmacokinetics (PK) of [64Cu]Cu-AKY-2519 and/or [225Ac]Ac-AKY-2519, as well as the preliminary anti-tumor activity of [225Ac]Ac-AKY-2519 in participants with metastatic castration-resistant prostate cancer (mCRPC) with and without prior exposure to 177Lu-PSMA-617 (PLUVICTO™).

This Phase 1b study consists of a dose escalation portion and a backfill portion. The dose escalation portion will investigate ascending doses of [225Ac]Ac-AKY-2519 across two cohorts enrolling in parallel:

• Cohort A: participants with metastatic castration-resistant prostate cancer (mCRPC) with NO prior exposure to 177Lu-PSMA-617 (PLUVICTO™) and
• Cohort B: participants with metastatic castration-resistant prostate cancer (mCRPC) with prior exposure to 177Lu-PSMA-617 (PLUVICTO™)

The backfill portion may enrich in two select dose levels from each cohort (Cohort A: mCRPC 177Lu-PSMA-617 (PLUVICTO™)-naïve; Cohort B: mCRPC 177Lu-PSMA-617 (PLUVICTO™)-experienced) to gather further information on the safety and efficacy and to determine the recommended phase 2 dose (RP2D) for each cohort.

Inclusion Criteria:

• Age ≥ 18 years
• Histologic or cytologic confirmation of prostatic adenocarcinoma
• ECOG Performance Status of 0 or 1
• Adequate end-organ function
• Ability to give informed consent and comply with study requirements
• Patients with CNS metastases are eligible if they have received therapy and are neurologically stable, asymptomatic and not receiving corticosteroids
• Castrate levels of serum testosterone (< 50 ng/dL)
• Documented disease progression on most recent prior line of therapy, either by PSA or imaging-based progression
• Cohort B: Received 2 or more prior doses of 177Lu-PSMA-617 (PLUVICTO)

Exclusion Criteria:

• Prior treatment with more than 2 Androgen receptor pathway inhibitors (ARPIs) and/or more than 1 taxane-based therapy in the mCRPC setting

• Prior treatment with a targeted radiotherapy

  o Exception: Cohort B is required to have had at least 2 prior doses of 177Lu-PSMA-617 (PLUVICTO)

• Prior treatment with a B7-H3 targeted therapy

• Received an investigational agent within the previous 28 days

• Impaired cardiac function or clinically significant cardiac disease

• Concurrent serious medical condition that would impair study participation or impact the assessment of treatment related toxicity