Phase Ib/IIa Dose Escalation and Expansion Study of [²¹²Pb]Pb-ADVC001 in Metastatic Prostate Cancer (TheraPb - Phase I/II Study).

This is a prospective, open-label, dose-escalation and randomized dose optimization and expansion study. The Phase Ib portion of the study aims to determine the safety and tolerability of escalating doses of [212Pb]Pb-ADVC001 administered every 6, 4, 2 or 1 week(s) and establish the recommended phase 2 doses (RP2D). The Phase 2a expansion aims to assess the efficacy and safety of [212Pb]Pb-ADVC001 at the RP2 doses in 3 participant groups.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Metastatic Castration-resistant Prostate Cancer; Metastatic Hormone Sensitive Prostate Cancer
• Intervention / Treatment: Drug: [²¹²Pb]Pb-ADVC001 (Phase 1b); Drug: [²¹²Pb]Pb-ADVC001 (Phase 2a)

Detailed Description

This is a single arm, non-randomized, toxicity and dose finding study. The trial will include a maximum of 18 patients with confirmed mCRPC and no prior history of radioligand therapy.

The study is based on a 3 + 3 design with 4 cohorts of patients receiving escalating doses 60, 90, 120 and 150MBq of [212Pb]Pb-ADVC001. Each patient in each cohort will be given the same dose and a maximum of 4 cycles of therapy administered at 6 weekly intervals.

The decision to recruit the next cohort of patients and escalate the dose will be made after reviewing all safety data from the previous cohort acquired over 6 weeks after the first cycle of therapy. In this manner, recruitment of the next cohort can occur before all treatment cycles have been administered to the previous cohort.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Anna Karmann; Phone Number: 612 8000 4199; Email: contact@advancell.com.au

Study Locations

• Australia
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Recruiting
      • Royal Brisbane & Women's Hospital
      • Principal Investigator: David Wyld
    • Brisbane, Queensland, Australia, 4102
      • Recruiting
      • Princess Alexandra Hospital
      • Principal Investigator: Aaron Hansen
    • Southport, Queensland, Australia, 4215
      • Recruiting
      • Gold Coast University Hospital
      • Principal Investigator: Robert Mason

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Documented metastatic adenocarcinoma of the prostate, confirmed by histopathology.

• Progressive metastatic prostate cancer demonstrated by at least one of the following:

  1. Increase in PSA greater than 25% and > 2 ng/mL above nadir, confirmed by progression at two timepoints at least three weeks apart
  2. Progressive disease or new lesion(s) (relative to previous imaging) in the viscera or lymph nodes as per the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or in bone as per Prostate Cancer Clinical Trials Working Group 3 (PCWG3).
• For Phase 1b Dose Escalation: Metastatic castration-resistant prostate cancer (mCRPC) with exposure to at least one ARPi and taxane-based chemotherapy at any time in the course of their disease (unless taxanes considered contraindicated or declined by participant as documented in the patient's source documents and eCRF).

• For Phase 2a Dose Expansion:

  1. Group 1: Metastatic hormone-sensitive prostate cancer (mHSPC) with a sub-optimal PSA response defined as PSA ≥ 0.2 ng/mL despite receiving androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPi) without evidence of disease progression
  2. Group 2: Progressive mCRPC post ≥ 1 ARPi; 177Lutetium (177Lu)-PSMA-naïve and not previously treated with chemotherapy for CRPC
  3. Group 3: Progressive mCRPC with prior exposure to 177Lu-PSMA and ARPi
• Has disease that is prostate specific membrane antigen (PSMA) positive, as demonstrated by ⁶⁸Ga-PSMA-PET/CT or ¹⁸F-based PSMA PET/CT and confirmed as eligible by local reader. PSMA-positive participants are defined as those having at least one tumor lesion with ⁶⁸Ga- or ¹⁸F- PSMA PET CT uptake greater than normal liver (based on visual assessment) and all tumor lesions larger than size criteria with ⁶⁸Ga- or ¹⁸F-PSMA uptake greater than liver [short axis size criteria: organs ≥ 1 cm, lymph nodes ≥ 2.5 cm, bones (soft tissue component) ≥ 1 cm].
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• Adequate haematological, renal, and liver function.

Key Exclusion Criteria:

• Has received prior systemic radioligand therapy with the exception of prior radium-223. Prior 177Lu-PSMA is required for Phase 2a Group 3 participants.
• Systemic anti-cancer therapy and/or radiation therapy within four weeks of C1D1 or has received any investigational agent within four weeks of C1D1.
• Has malignancies other than prostate cancer within 3 years prior to enrolment, except for those with a negligible risk of metastases
• Known CNS metastases or symptoms of spinal cord compression or impending spinal cord compression. Patients with prior treatment for spinal cord compression should be clinically stable off steroids for at least 4 weeks.
• Has diffuse bone-marrow involvement, i.e, "superscan", defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake.
• Has a serious active or sub-clinical infection, or angina pectoris, or heart failure (New York Heart Association [NYHA] Class III or IV), or significantly prolonged QT interval, or other serious illness which might impair the ability to participate in this study to the full extent, or which may require treatment that could interact with study treatment.
• Has a known alteration in breast cancer genes (BRCA) BRCA1 or BRCA2 and are eligible to receive poly ADP ribose polymerase (PARP) inhibitor therapy according to their treating institution's standard of care.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b; Phase 1b Dose Escalation: Participants with PSMA-positive mCRPC who have had exposure to at least one ARPi and taxane-based chemotherapy (unless taxanes contraindicated or declined) at any time in the course of their disease.	Drug: [²¹²Pb]Pb-ADVC001 (Phase 1b); Ph1b Escalation Drug: [²¹²Pb]Pb-ADVC001administered intravenously per dose escalation scheme Dose Level 1 - 60 MBq, 4 cycles every 6 weeks Dose Level 2a - 120 MBq, 4 to 6 cycles every 4 weeks Dose Level 2b - Optional cohort of 120 MBq, 4 to 6 cycles every 2 weeks Dose Level 3a - 160 MBq, 4 to 6 cycles every 4 weeks Dose Level 3b - Optional cohort of 160 MBq, 4 to 6 cycles every 2 weeks Dose Level 3c - Optional cohort of 160 MBq, 4 to 6 cycles every week Dose Level 4a; 200 MBq, 4 to 6 cycles every 4 weeks Dose Level 4b - Optional cohort of 200 MBq, 4 to 6 cycles every 2 weeks Dose Level 4c - Optional cohort of 200MBq, 4 to 6 cycles every week
Experimental: Phase 2a; Group 1: Participants with PSMA-positive mHSPC with PSA ≥ 0.2 ng/mL despite androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPi) without evidence of disease progression Group 2: Participants with PSMA-positive mCRPC who have had exposure to at least one ARPi at any time in the course of their disease and has not received a taxane for the treatment of mCRPC. Group 3: Participants with PSMA-positive mCRPC who have had exposure to at least one ARPi and to 177Lu-PSMA at any time in the course of their disease.	Drug: [²¹²Pb]Pb-ADVC001 (Phase 2a); Ph2a Expansion Drug: All participants are randomized 1:1 to receive either 160 or 200 MBq of ADVC001. Each participant receives up to 12 doses according to an adaptive dosing schedule and rules allowing for a treatment pause ('treatment holiday') with the possibility of subsequent therapy restarts. All participants continue ADT throughout the study. Group 1 participants receive ongoing ARPi as per standard of care, and Group 2 participants also are randomized to receive ADVC001 ± concomitant ARPi.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RP2D (Phase 1b)	Incidence and severity of dose-limiting toxicities, as defined in Section 6.5 of the protocol and assessed in accordance with NCI CTCAE Version 5.0. Incidence and severity of adverse events, SAEs and radiation adverse events of special interest, assessed in accordance with NCI CTCAE Version 5.0.	Up to 60 Months
Therapeutic efficacy as assessed by PSA response (Phase 1b/2a)	PSA response defined as a reduction from baseline PSA level of at least 50% (PSA 50) and 90% (PSA 90), confirmed by a follow-up PSA.	Up to 60 months
Therapeutic efficacy as assessed by objective response rate and disease control rate (Phase 1b/2a)	Objective response rate (OCR) and disease control rate (DCR) derived from CT imaging based on RECIST 1.1 and Prostate Cancer Trials Working Group 3.	Up to 60 months
Therapeutic efficacy as assessed by radiographic progression-free survival (Phase 1b/2a)	Radiographic progression-free survival (rPFS) defined as the time from date of first dosing to the occurrence of one of the following: 1. Progression of measurable lesions using RECIST 1.1. 2. Progression of bone lesions using Prostate Cancer Working Group 3 criteria. 3. Death due to any cause.	Up to 60 months
Therapeutic efficacy as assessed by progression-free survival (Phase 1b/2a)	Progression-free survival defined as the time from date of first dosing to the occurrence of one of the following: 1. Radiographic progression per RECIST 1.1 or bone scan in accordance with PCWG3 criteria. 2. Clinical progression as determined by investigator assessment. 3. PSA progression defined by PCWG3. 4. Death due to any cause.	Up to 60 months
Therapeutic efficacy as assessed by overall survival (Phase 1b/2a)	Overall survival defined as the time from date of first dosing to death from any cause.	Up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD) (Phase 1b)	Incidence and severity of dose-limiting toxicities, as defined in Section 6.5 of the protocol and assessed in accordance with NCI CTCAE Version 5.0.	Up to 60 months
Safety and Tolerability (Phase 1b/2a)	Incidence and severity of adverse events, SAEs and radiation adverse events of special interest, assessed in accordance with NCI CTCAE Version 5.0.	Up to 60 months
Dosimetry (Phase 1b/2a)	Absorbed radiation doses (expressed as Gy/MBq) of administered [²¹²Pb]Pb-ADVC001 to organs at risk and tumor lesions.	Day 1 of the first cycle through to the end of treatment (28 days after administration of the last treatment cycle).
Time to next non-study anti-cancer treatment from completion of [²¹²Pb]Pb-ADVC001 treatment (Phase 2a)	Median time to commencement of next (non-study) anti-cancer treatment following completion of [²¹²Pb]Pb-ADVC001 treatment	Up to 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biodistribution (Phase 1b/2a)	Biodistribution of [²¹²Pb]Pb-ADVC001 on SPECT/CT and [⁶⁸Ga]Ga-PSMA (or [¹⁸F]F-based-PSMA) on PET/CT as determined by image analysis and interpretation by expert readers.	Up to 24 weeks
PSMA PET response (Phase 1b/2a)	[⁶⁸Ga]Ga- or [¹⁸F]F-based PSMA responses based on the Consensus Statement on PSMA PET Response Assessment Criteria in Prostate Cancer.	Up to 24 weeks
Biomarkers of immune activation (Phase 1b/2a)	Change from baseline in biomarkers of immune activation and efficacy endpoints including PSA response and ORR.	Up to 32 weeks
PK parameter: Maximum observed concentration (Cₘₐₓ) of [²¹²Pb]Pb-ADVC001 in blood (Phase 1b/2a)		On the first and second day of study treatment
PK parameter: Time to maximum observed concentration (Tₘₐₓ) of [²¹²Pb]Pb-ADVC001 in blood (Phase 1b/2a)		On the first and second day of study treatment
PK parameter: Area under the concentration-time curve (AUC) of [²¹²Pb]Pb-ADVC001 in blood (Phase 1b/2a)		On the first and second day of study treatment
PK parameter: Clearance of [²¹²Pb]Pb-ADVC001 in blood (Phase 1b/2a)		On the first and second day of study treatment
PK parameter: Amount of [212Pb]Pb-ADVC001 eliminated in urine (Phase 1b/2a)		On the first and second day of study treatment
PK parameter: [212Pb]Pb-ADVC001 metabolites in urine (Phase 1b/2a)		On the first and second day of study treatment
Exploratory [212Pb]Pb PET/CT imaging (Phase 1b/2a)	Biodistribution of [212Pb]Pb-ADVC001 via [212Pb]Pb PET/CT.	Up to 5 weeks

Collaborators and Investigators

• Sponsor: AdvanCell Pty Limited
• Investigators: Principal Investigator: Aaron Hansen, Princess Alexandra Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2023
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): June 1, 2029

Study Registration Dates

• First Submitted: January 7, 2023
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): February 20, 2026
• Last Update Submitted That Met QC Criteria: February 18, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: PSMA-AC-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No