A Phase 1/2a Study to Evaluate the Safety, Tolerability, Whole-Body Distribution, and Preliminary Clinical Activity of 161Tb-RAD402, a Radiolabeled Anti-Kallikrein-Related Peptidase 3 (KLK3) Monoclonal Antibody Targeting Free Prostate-Specific Antigen, in Participants With Castration-Resistant Prostate Cancer (CRPC)
Overview
- Phase
- Phase 1
- Intervention
- 161Tb RAD402
- Conditions
- Not specified
- Sponsor
- Radiopharm Theranostics, Ltd
- Enrollment
- 73
- Locations
- 1
- Primary Endpoint
- Incidence of treatment emergent adverse events of 161Tb RAD402 (phase 1) (Safety)
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
A Phase 1/2a Study to Evaluate the Safety, Tolerability, Whole-Body Distribution, and Preliminary Clinical Activity of 161Tb-RAD402, a Radiolabeled Anti-KLK3 Monoclonal Antibody Targeting Free Prostate-Specific Antigen, in Participants with Castration-Resistant Prostate Cancer (CRPC).
Detailed Description
The purpose of this study is to establish the safety profile, biodistribution, pharmacokinetics (PK), and radiation dosimetry of 161Tb-RAD402, to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), and to evaluate preliminary anti-tumor activity in participants with locally advanced or metastatic Castration-Resistant Prostate Cancer (CRPC). The study is divided into 2 phases. Phase 1 is the dose escalation phase to establish the safety profile of 161Tb-RAD402 and to determine the MTD and/or RP2D of 161Tb-RAD402 using a Bayesian Optimal Interval (BOIN) design. Phase 2a is the dose expansion phase at the RP2D to confirm the safety of the MTD and/or RP2D and to evaluate preliminary anti-tumor activity of 161Tb-RAD402 using a probability of success design for Prostate Specific Antigen (PSA)50 based on a Bayesian beta-binomial design. Participants ≥ 18 years of age with CRPC who have documented disease progression during or after their most recent line of anticancer therapy will be eligible to enroll. Each phase consists of a Screening Period, a Treatment and Imaging Period, and a Safety and Long-term Follow-up Period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures.
- •Male participants ≥ 18 years of age.
- •Participants with a documented history of histopathologically confirmed locally advanced or metastatic CRPC defined as follows:
- •Progressive CRPC defined as castrate levels of testosterone and progressing by at least one of the following criteria:
- •Serum PSA increase \>25% and \>2.0 ng/ml above nadir, confirmed by progression at 2 timepoints at least 3 weeks apart (PCWG3)
- •Soft tissue progression defined as a ≥20% increase in the sum of the diameter (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest sum of the diameter since the previous treatment was started or the appearance of one or more new lesions by computed tomography (CT)/ magnetic resonance imaging (MRI).
- •Progression of bone disease defined by PCWG3 as evaluable disease or new bone lesions by bone scan (if metastatic disease).
- •Identification of new soft tissue or bone lesions on PSMA PET imaging.
- •If metastatic disease, metastatic disease defined as either or both of the following:
- •Documented M1 disease on conventional imaging (CT/MRI of the chest/abdomen/pelvis and/or Technetium 99m \[99mTc\] whole-body bone scan)
Exclusion Criteria
- •Prostate cancer with known significant sarcomatoid, or spindle cell, or neuroendocrine small cell components, or metastasis of other cancer to the prostate.
- •History of prior organ transplant (other than corneal transplant)
- •Any other known, active malignancy except for non-melanoma skin cancer or adequately treated non-muscle-invasive urothelial carcinoma of the bladder (i.e. tumor in situ (Tis), tumor grade a (Ta) and low-grade tumor grade 1 (T1) tumors). Participants with a history of malignancies of low recurrence potential who have received curative-intent therapy may be approved on a case-by-case basis in discussion with the Sponsor, if it is determined not to put the participant at an increased risk of adverse drug effects and/or interfere with the integrity of the study outcome.
- •Have any medical condition that would, in the Investigator's judgment, prevent the participant's full participation in the clinical study due to safety concerns or compliance with clinical study procedures such as participants with severe claustrophobia who are unresponsive to oral anxiolytics, participants with low back pain who cannot lie comfortably on an imaging table, participants who are hyperactive or hyperkinetic such that they cannot tolerate lying still for multiple time point imaging procedures, etc.
- •Residual toxicity ≥ Grade 2 from prior anti-cancer therapy (except alopecia and peripheral sensory neuropathy).
- •History of uncontrolled allergic reactions and/or known or expected hypersensitivity to protein therapeutics, 161Tb-RAD402, or any of its excipients.
- •Inadequate organ functions as reflected in laboratory parameters:
- •Estimated glomerular filtration rate (eGFR) \< 50 mL/min adjusted for body surface area (BSA) using the Chronic Kidney Disease Epidemiology Collaboration formula
- •Platelet count of \< 100 x 109/L
- •Absolute neutrophil count (ANC) \< 1.5 x 109/L
Arms & Interventions
161Tb RAD402
Single-arm, open-label study of 161Tb RAD402 consisting of Phase 1 Dose Escalation and Phase 2 Dose Expansion study parts.
Intervention: 161Tb RAD402
Outcomes
Primary Outcomes
Incidence of treatment emergent adverse events of 161Tb RAD402 (phase 1) (Safety)
Time Frame: 6 weeks
As defined per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Recommended dose(s) of 161Tb RAD402 for future exploration (phase 1)
Time Frame: 6 weeks
Incidence of dose-limiting toxicities (DLTs) during the first 6 weeks following the first 161Tb RAD402 injection
Preliminary anti-tumor activity, as defined by biochemical response, in participants who are treated with 161Tb RAD402 at the RP2D (phase 2a)
Time Frame: Up to 30 weeks
Proportion of participants who achieve a ≥50% decline in prostate-specific antigen (PSA) 50
Secondary Outcomes
- Preliminary anti-tumor activity of 161Tb RAD402 (phase 1)(Up to 30 weeks)
- Preliminary anti-tumor activity of 161Tb RAD402 as defined by biochemical response (phase 1)(Up to 30 weeks)
- Pharmacokinetics of 161Tb RAD402 (phase 1)(120 hours)
- Radiation dosimetry of 161Tb RAD402 (phase 1)(120 hours)
- Biodistribution of 161Tb RAD402 (phase 1)(120 hours)
- Preliminary anti-tumor activity of 161TbRAD402 at the RP2D in participants with Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) positive CRPC previously treated with ≥1 Androgen Receptor Signalling Inhibitor (ARSI) (phase 2a)(Up to 30 weeks)
- Incidence of treatment emergent adverse events of 161Tb RAD402 at the RP2D (phase 2a) (safety and tolerability)(6 weeks)
- Pharmacokinetics of 161Tb RAD402 at the RP2D (phase 2a)(120 hours)
- Radiation dosimetry of 161Tb RAD402 at the RP2D (phase 2a)(120 hours)
- Biodistribution of 161Tb RAD402 at the RP2D (phase 2a)(120 hours)
- Preliminary anti-tumor activity, of 161Tb RAD402 at the RP2D in participants with PSMA PET-positive CRPC who were previously treated with at least one ARSI by comparing the Radiographic progression free survival (rPFS) (phase 2a)(Up to 30 weeks)