[Ac-225]-PSMA-62 Trial in Oligometastatic Hormone Sensitive and Metastatic Castration Resistant Prostate Cancer (ACCEL)

[Ac-225]-PSMA-62 Phase I/II Clinical Trial to Characterize Efficacy, Safety, Tolerability, and Dosimetry in Oligometastatic Hormone Sensitive and Metastatic Castration Resistant Prostate Cancer (ACCEL)

ACCEL is a multicenter, open label phase Ia/Ib/II study of [Ac-225]-PSMA-62 in participants with prostate-specific membrane antigen (PSMA)-positive prostate cancer.

Study Overview

• Status: Active, not recruiting
• Conditions: Prostate Cancer; Metastatic Castration-resistant Prostate Cancer; Oligometastatic Prostate Carcinoma; Hormone Sensitive Prostate Cancer
• Intervention / Treatment: Drug: [Ac-225]-PSMA-62 (OmHSPC); Drug: [Ac-225]-PSMA-62 (mCRPC)

Detailed Description

The primary aim of the phase Ia study is to evaluate the safety and tolerability of [Ac-225]-PSMA-62 to determine the maximum tolerated dose (MTD). The primary aim of the randomized phase Ib dose optimization is to determine the recommended phase II doses (RP2D) for patients with mCRPC and OmHSPC. The aim of the phase II study for patients with mCRPC is to evaluate the efficacy of [Ac-225]-PSMA-62.

• Study Type: Interventional
• Enrollment (Estimated): 142
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Hamilton, Canada, L8V 5C2
    • Juravinski
  • Montreal, Canada, H3T 1E2
    • Jewish General Hospital
  • Montreal, Canada, H4A 3J1
    • McGill University
  • Québec, Canada, G1J 1Z4
    • Centre Hospitalier Universite de QUEBEC
  • Saguenay, Canada, G7H 5H6
    • Hopital de Chicoutimi
  • Toronto, Canada, M5G 2M9
    • Princess Margaret Cancer Centre
  • Vancouver, Canada, V5Z4E6
    • BC Cancer Vancouver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate
2. ECOG performance status 0 to 1

3. Criteria specific for patients with mCRPC:

   1. Previously received an androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy (unless ineligible or refused taxane). Received a maximum of 3 prior systemic therapy regimens in the mCRPC setting

   2. Progressive mCRPC at the time of consent based on at least 1 of the following criteria being met in the context of castrate levels of testosterone:

      • PSA progression defined as rising PSA values at a minimum of 1-week intervals, with the last result being at least 1.0 ng/mL
      • Soft-tissue progression defined as an increase ≥20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions
      • Progression of bone disease defined as the appearance of two or more new lesions by bone scan
   3. At least one PSMA-PET positive lesion for prostate cancer
   4. Castrate circulating testosterone levels (<1.74 nmol/L or <50 ng/dL)

4. Criteria specific for patients with OmHSPC:

   1. PSA recurrence after radical prostatectomy (RP) or definitive radiation therapy (RT), with or without adjuvant/salvage local therapy (radiation or surgery), with or without (neo)adjuvant ADT

      • PSA ≥ 0.2ng/mL for patients with prior RP +/- RT, or
      • PSA of ≥ 2 ng/mL above nadir for patients with only prior RT
   2. 1- 5 PSMA-PET positive lesions identified outside the prostate bed or remaining gland.

Exclusion Criteria:

1. Patient has received any other investigational therapeutic agents within 4 weeks or 5 half-lives (whichever is shorter) of starting the study treatment
2. Evidence of ongoing and untreated urinary tract obstruction
3. Existing Grade 1 dry mouth (xerostomia) or symptomatic Grade 1 dry eye (xerophthalmia) for any reason
4. Patient has any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while on the study or that could confound discrimination between disease- and study treatment-related toxicities

5. Criteria specific for patients with mCRPC:

   1. Patient has received any PSMA-directed radioligand therapy (e.g., Lu-177-PSMA, Lu-177-PNT2002, Ac-225-J591)
   2. Patient has received any therapeutic systemic radionuclides (e.g., radium-223, rhenium-186, strontium-89), or non-PSMA-directed therapeutic radioligands (e.g., Lu-177-Dotatate) within 5 half-lives of starting the study treatment

6. Criteria specific for patients with OmHSPC:

   1. Patient has received any systemic anti-cancer therapy for prostate cancer with the exception of (neo)adjuvant ADT for management of localized disease
   2. Presence of any liver metastases
   3. Known presence of central nervous system metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: OmHSPC; Patients with prostate cancer and biochemical recurrence after definitive surgery or radiation therapy, with 1-5 PSMA-positive lesions, who have not yet initiated lifelong hormone therapy.	Drug: [Ac-225]-PSMA-62 (OmHSPC); Phase Ia: Administered intravenously per dose escalation scheme. Patients will receive a single dose of [Ac-225]-PSMA-62 on Day 1 of each 8-week cycle for up to 2 cycles. Phase Ib: Administered intravenously at MTD or one dose level below MTD. Patients will receive a single dose of [Ac-225]-PSMA-62 on Day 1 of each 8-week cycle, for a total of 2 cycles.
Experimental: mCRPC; Patients with PSMA-positive mCRPC who have prior treatment with at least one APRI and received taxane chemotherapy (or ineligible/refused); and received a maximum of 3 prior systemic therapy regimens in the mCRPC setting.	Drug: [Ac-225]-PSMA-62 (mCRPC); Phase Ia: Administered intravenously per dose escalation scheme. Patients will receive a single dose of [Ac-225]-PSMA-62 on Day 1 of each 6-week cycle for up to 4 cycles. Phase Ib: Administered intravenously at MTD or one dose level below MTD. Patients will receive a single dose of [Ac-225]-PSMA-62 on Day 1 of each 6-week or 4-week cycle, for a total of 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	Phase Ia: Incidence of dose limiting toxicities (DLTs)	From first dose of study drug through end of DLT period (4 weeks)
Safety, tolerability, and Recommended Phase II Dose (RP2D)	Phase 1b: Incidence and severity of treatment emergent adverse events (TEAEs)	From first dose of study drug through end of treatment (~16 - 24 weeks)
Safety and tolerability	Phase Ia: Incidence and severity of treatment emergent adverse events (TEAEs)	From first dose of study drug through end of treatment (~16 - 24 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of treatment emergent adverse events as assessed per CTCAE v5.0	To assess safety and tolerability of [Ac-225]-PSMA-62	From first dose of study drug through end of study (~5 years)
Absorbed dose estimates (Gy) in normal organs	Evaluation of the biodistribution and radiation dosimetry of [Ac-225]-PSMA-62 to normal organs	From first dose of study drug through end of treatment (~16 - 24 weeks)
The proportion of patients with a PSA change from baseline	To determine the effect of [Ac-225]-PSMA-62 on prostate-specific antigen (PSA) kinetics	From first dose of study drug through efficacy follow-up period (up to approximately 3 years)
Time to initiation of any life-long ADT, or other systemic hormonal therapies for prostate cancer	OmHSPC only: Preliminary efficacy assessment	From first dose of study drug through end of study (~5 years)
Objective Response Rate (ORR)	mCRPC only: Percentage of participants with a complete response (CR) or partial response (PR)	From first dose of study drug until disease progression (up to approximately 3 years)
Radiographic progression free survival (rPFS)	Phase Ib mCRPC only: rPFS per investigator assessment	From first dose of study drug until disease progression (up to approximately 3 years)
Patient Reported Outcome (PRO) - Pain	Phase Ib only: Measured by the change on the Brief Pain Inventory Short Form (BPI-SF) questionnaire, scored from 0 ('No pain', 'Does not interfere') to 10 ('Pain as bad as you can imagine', 'Completely interferes') on the severity and interference on daily functions of pain.	From first dose of study drug until disease progression (up to approximately 3 years)
Patient Reported Outcome (PRO) - Impact of treatment toxicity	Phase Ib only: Measured by the change the Functional Assessment of Cancer Therapy (FACT-Item GP5) questionnaire, scored from 0 ('Not at all') to 4 ('Very much') on the interference of symptoms related to treatment emergent adverse events.	From first dose of study drug until disease progression (up to approximately 3 years)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Collaborators: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 1, 2032

Study Registration Dates

• First Submitted: January 3, 2024
• First Submitted That Met QC Criteria: January 19, 2024
• First Posted (Actual): January 29, 2024

Study Record Updates

• Last Update Posted (Actual): December 22, 2025
• Last Update Submitted That Met QC Criteria: December 19, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: mCRPC; Radioligand Therapy; Castration Resistant Prostate Cancer; Prostatic Neoplasms; Genital Neoplasms, Male; Radiopharmaceuticals; Actinium; Urogenital Neoplasm; Hormone Sensitive Prostate Cancer; Oligometastatic Prostate Cancer; [225Ac]-PSMA-62; Ac-225-PSMA-62; OmHSPC
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Prostatic Neoplasms; Urogenital Neoplasms; Genital Neoplasms, Male
• Other Study ID Numbers: 27197; J5N-OX-JJEA (Other Identifier: Eli Lilly and Company)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No