ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12625001362482

Ethics application status

Approved

Date submitted

4/11/2025

Date registered

5/12/2025

Date last updated

5/12/2025

Date data sharing statement initially provided

5/12/2025

Type of registration

Prospectively registered

Titles & IDs

Public title

Phase 1 trial of a novel antibody-targeted radiotherapy in patients with metastatic castrate-resistant prostate cancer (mCRPC)

Scientific title

Phase 1 trial of a novel HER3 antibody-targeted radiotherapy (ATNM-400 [225Ac]-barecetamab-DOTA) in patients with metastatic castrate-resistant prostate cancer

Additional trial identifiers [1]

Protocol No.: ATNM-400-1301 / IND 175163

Universal Trial Number (UTN)

Trial acronym

Related trial records

Health condition

Health condition(s) studied:

Metastatic Castrate-Resistant Prostate Cancer (mCRPC)

Condition category

Condition code

Cancer

Prostate

Intervention/exposure

Study type

Interventional

Description of the intervention or exposure

This is a 3-part, multicentre, open-label Phase 1 study of ATNM-400, a HER3-targeted radiotherapy, in men with metastatic castrate-resistant prostate cancer (mCRPC).

Part A – Imaging Lead-in ([89Zr]-barecetamab-DFO):
Up to 10 participants will receive a single intravenous (IV) dose of [89Zr]-barecetamab-DFO at approximately 37 MBq (1 mCi) for imaging-only purposes. This radiolabelled antibody is a non-therapeutic surrogate of ATNM-400 and is used to assess tumor targeting, biodistribution, dosimetry, and pharmacokinetics. PET/CT imaging will be performed at multiple time points (2–336 hours post-dose) to determine organ and tumor uptake and confirm radiation safety for subsequent therapeutic dosing.
All imaging doses will be prepared and administered by qualified nuclear medicine personnel (radiopharmacists, radiologists, or technologists) at participating sites in compliance with radiation safety regulations

Part B – ATNM-400 Dose Escalation:
Eligible participants will receive ATNM-400 ([225Ac]-barecetamab-DOTA) as an intravenous infusion on Day 1 of each 42-day treatment cycle, for up to four cycles. Dose escalation will follow a traditional 3+3 design across five planned cohorts, with dose levels ranging from 1.0 µCi/kg (0.037 MBq/kg) to 3.0 µCi/kg (0.11 MBq/kg). The infusion will be administered over approximately 30 minutes. Dose-limiting toxicities (DLTs) will be evaluated by the Safety Review Committee (SRC) to determine the maximum tolerated dose. Participants from Part A who demonstrate tumour uptake and meet eligibility criteria may re-enroll into Part B.

Part C – ATNM-400 Dose Expansion:
Approximately 18 participants will receive ATNM-400 at the maximum tolerated dose (MTD) determined in Part B. Part C will begin after the final participant in Part B has completed the DLT observation period and the SRC has confirmed the MTD, which is typically within two to four weeks after the last Part B participant’s DLT window. Participants from Part B will not be re-treated in Part C; only newly enrolled participants will receive expansion dosing. ATNM-400 will be administered as an intravenous infusion on Day 1 of each 42-day treatment cycle for up to four cycles. Each cycle may be extended to 56 days if additional time is required for hematologic recovery, although dosing will continue to occur once per cycle regardless of cycle length.

Intervention code [1]

Treatment: Drugs

Description of the comparator or control

No control group – open-label dose escalation

Control group

Uncontrolled

Outcomes

Primary outcome [1]

(Part A) Dosimetry of [89Zr]-barecetamab-DFO

Timepoint [1]

(Part A) Imaging at approximately 2–4 hours, 72–96 hours, 120–144 hours, 168–192 hours, and 240–336 hours after a single intravenous dose (up to 14 days post-dose).

Primary outcome [2]

(Part B & C) Incidence of treatment-emergent adverse events (TEAEs)

Timepoint [2]

From first dose through 30 days after the final dose.

Primary outcome [3]

(Part A) Pharmacokinetics of [89Zr]-barecetamab-DFO

Timepoint [3]

Blood samples collected pre-dose and at approximately 5 minutes, 30 minutes, 1 hour, 2–4 hours, 72–96 hours, 120–144 hours, 168–192 hours, and 240–336 hours post-dose

Secondary outcome [1]

Proportion of participants achieving a greater than or equal to 30% reduction in prostate-specific antigen (PSA) from baseline.

Timepoint [1]

Every 4 weeks during treatment, and at monthly follow-up visits for up to 12 months after the last dose.

Secondary outcome [2]

(Part B & C): Incidence of dose-limiting toxicities (DLTs) (Note: This is a primary outcome)

Timepoint [2]

During the first 6 weeks (42 days) after the first dose of ATNM-400, corresponding to one full treatment cycle

Secondary outcome [3]

Objective response rate (ORR) assessed using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), evaluated in Parts B and C of the study.

Timepoint [3]

Every 8 weeks from baseline until disease progression or end of study (up to 12 months after last dose).

Secondary outcome [4]

Duration of response (DoR) assessed using RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) criteria, evaluated in Parts B and C of the study.

Timepoint [4]

Assessed at each scheduled imaging visit every 8 weeks until 12 months after the last dose, and at study completion.

Secondary outcome [5]

Radiographic progression-free survival (rPFS) assessed using Prostate Cancer Working Group 3 (PCWG3) criteria, evaluated in Parts B and C of the study.

Timepoint [5]

From date of first dose to radiographic progression or death, whichever occurs first (evaluated every 8 weeks).

Secondary outcome [6]

Overall survival (OS), evaluated in Parts B and C of the study.

Timepoint [6]

From date of first dose until death from any cause (assessed quarterly for up to 12 months after last dose).

Secondary outcome [7]

Proportion of participants achieving a greater than or equal to 50% reduction in PSA from baseline (PSA50 response).

Timepoint [7]

Every 4 weeks during treatment, and at monthly follow-up visits for up to 12 months after the last dose.

Secondary outcome [8]

Proportion of participants achieving a greater than or equal to 90% reduction in PSA from baseline (PSA90 response).

Timepoint [8]

Every 4 weeks during treatment, and at monthly follow-up visits for up to 12 months after the last dose.

Eligibility

Key inclusion criteria

Adults aged 18 years and older with histologically confirmed metastatic castrate-resistant prostate cancer (mCRPC) and a positive HER3 PET/CT scan. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Life expectancy greater than 6 months. Prior androgen deprivation therapy (ADT) with or without a taxane. Adequate organ function. Recovered from all prior treatment-related toxicities to less than Grade 1 severity.

Minimum age

18 Years

Maximum age

No limit

Sex

Males

Healthy volunteers

Key exclusion criteria

Urinary obstruction with catheter; prior HER3-targeted radiotherapy; recent chemo / investigational drug < 28 days; severe comorbidity (CHF III/IV, active infection, hep B/C); CNS metastases unless stable; superscan on bone scan

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Phase 1

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

13/12/2025

Actual

Date of last participant enrolment

Anticipated

6/11/2027

Actual

Date of last data collection

Anticipated

8/11/2028

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,SA,WA,VIC

Recruitment outside Australia

Country [1]

United Kingdom

State/province [1]

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Actinium Pharmaceuticals Inc.

Address [1]

Country [1]

United States of America

Primary sponsor type

Commercial sector/Industry

Name

Actinium Pharmaceuticals Australia Pty Limited

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Human Research Ethics Committee G

Ethics committee address [1]

https://bellberry.com.au/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

02/09/2025

Approval date [1]

07/10/2025

Ethics approval number [1]

Summary

Brief summary

This study aims to understand how a new anti-cancer drug ATNM-400 ([²²5Ac]-barecetamab-DOTA) behaves in the body, to determine a safe dose range, and to assess its early signs of anti-tumour activity.

Who is it for?
You may be eligible for this study if you are aged 18 years or older, you have been diagnosed with metastatic prostate cancer that has not responded to surgery and you have undergone at least one previous round of chemotherapy.

Study details
Participants who choose to enrol in this study may be invited to participate in one of three parts.
Part A - participants will have a dose of [89Zr]-barecetamab-DFO injected into a vein and will then undergo PET-CT imaging. These participants will also be asked to provide blood samples for up to 6 hours after their injection.

Part B - participants will be given a dose of ATNM-400 ([²²5Ac]-barecetamab-DOTA) injected into a vein once every 6 weeks. If participants don't experience any extreme side effects, they may have this treatment repeated up to 4 times. Different groups of participants will be enrolled to assess higher doses of ATNM-400 ([²²5Ac]-barecetamab-DOTA) for this part.

Part C - participants will be give a dose of ATNM-400 ([²²5Ac]-barecetamab-DOTA) injected into a vein once every 6 weeks. If participants don't experience any extreme side effects, they may have this treatment repeated for up to 1 year.

Participants in Part B and C will also be asked to provide further blood samples while receiving ATNM-400 and to undergo additional PET-CT and possibly MR imaging.

It is hoped this research will determine if ATNM-400 anti-cancer treatment could be developed further for patients with advanced prostate cancer who have limited treatment options.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Joe Cardaci

Address

St John of God Murdoch Hospital, 100 Murdoch Drive, Murdoch, WA, 6150, Australia

Country

Australia

Phone

+61 08 9366 1500

Fax

[email protected]

Contact person for public queries

Name

Dr. Dhiren Patel

Address

Actinium Pharmaceuticals Inc. 100 Park Avenue, 16th Floor New York, NY 10017 United States of America

Country

United States of America

Phone

+1 646 612 1223

Fax

[email protected]

Contact person for scientific queries

Name

Dr. Dhiren Patel

Address

Actinium Pharmaceuticals Inc. 100 Park Avenue, 16th Floor New York, NY 10017 United States of America

Country

United States of America

Phone

+1 646 612 1223

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

What supporting documents are/will be available?

Type	Citation	Link	Email	Other Details	Attachment
Ethical approval					ApprovalLetter-HREC2025-08-1392.pdf

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically