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.
Age
18–any
Sex
MALE
Healthy volunteers
Not accepted
You may be eligible if
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
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)
You may not be if
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
