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

NCT05720130 | Recruiting Phase 1

• 1 other identifier: PSMA-AC-01
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Metastatic Castration-resistant Prostate Cancer; Metastatic Hormone Sensitive Prostate Cancer; Prostate Cancer

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (4)

• Maximum tolerated dose (MTD) (Phase 1b)

  Up to 60 months

• Safety and Tolerability (Phase 1b/2a)

  Up to 60 months

• Dosimetry (Phase 1b/2a)

  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)

  Up to 60 months

Other Outcomes (10)

• Biodistribution (Phase 1b/2a)

  Up to 24 weeks

• PSMA PET response (Phase 1b/2a)

  Up to 24 weeks

• Biomarkers of immune activation (Phase 1b/2a)

  Up to 32 weeks

Study Arms (2)

Phase 1b

EXPERIMENTAL

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)

Phase 2a

EXPERIMENTAL

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)

Interventions

[²¹²Pb]Pb-ADVC001 (Phase 1b) DRUG

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

Phase 1b

[²¹²Pb]Pb-ADVC001 (Phase 2a) DRUG

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.

Phase 2a

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented metastatic adenocarcinoma of the prostate, confirmed by histopathology.
• Progressive metastatic prostate cancer demonstrated by at least one of the following:
• Increase in PSA greater than 25% and \> 2 ng/mL above nadir, confirmed by progression at two timepoints at least three weeks apart
• 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:
• 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
• Group 2: Progressive mCRPC post ≥ 1 ARPi; 177Lutetium (177Lu)-PSMA-naïve and not previously treated with chemotherapy for CRPC
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AdvanCell Pty Limited: lead

Study Sites (3)

Royal Brisbane & Women's Hospital

Brisbane, Queensland, 4029, Australia

RECRUITING

Princess Alexandra Hospital

Brisbane, Queensland, 4102, Australia

RECRUITING

Gold Coast University Hospital

Southport, Queensland, 4215, Australia

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Aaron Hansen

  Princess Alexandra Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Karmann

CONTACT

612 8000 4199; contact@advancell.com.au

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2023
• First Posted: February 9, 2023
• Study Start: March 15, 2023
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): June 1, 2029
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)