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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
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
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.
Royal Brisbane & Women's Hospital
Brisbane, Queensland, Australia
RECRUITINGPrincess Alexandra Hospital
Brisbane, Queensland, Australia
RECRUITINGGold Coast University Hospital
Southport, Queensland, Australia
RECRUITINGRP2D (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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 60 months
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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: Up to 60 months
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