A Phase 1, First-in-Human, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of [225Ac]Ac-FL-020 in Participants With mCRPC.
Overview
- Phase
- Phase 1
- Intervention
- [225Ac]Ac-FL-020
- Conditions
- Metastatic Castration-resistant Prostate Cancer
- Sponsor
- Full-Life Technologies GmbH
- Enrollment
- 50
- Locations
- 12
- Primary Endpoint
- Dose escalation: Incidence of Dose-Limiting Toxicities (DLTs).
- Status
- Recruiting
- Last Updated
- 3 months ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety, therapeutic effect, and pharmacokinetics of [225Ac]Ac-FL-020 in participants with metastatic castration-resistant prostate cancer (mCRPC).
Detailed Description
The aim of this Phase 1, First-in-Human, Open-label Trial is to evaluate the safety, tolerability, pharmacokinetics, and efficacy of \[225Ac\]Ac-FL-020 as a single agent in participants with metastatic Castration-Resistant Prostate Cancer (mCRPC). \[111In\]In-FL-020 serves as a surrogate for 225Ac-FL-020 for dosimetry purposes. The trial is divided into two parts: dose escalation in Part 1 and cohort expansion in Part 2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed metastatic CRPC.
- •Age ≥ 18 years.
- •Signed informed consent, and able and willing to comply with protocol requirements prior to any study procedures.
- •Patients must have a life expectancy \>3 months.
- •All patients are required to have one or more positive lesions detected by PSMA-PET/CT scan
- •Documented progression of the disease based on the Investigator judgement
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Have a castrate serum testosterone \< 50 ng/dL or \<1.7 nmol/L. Patients must continue primary androgen deprivation with an LHRH analogue (agonist/antagonist) if they have not undergone bilateral orchiectomy.
- •Have previously been treated with at least one of the following:
- •Androgen receptor signaling inhibitor (such as enzalutamide).
Exclusion Criteria
- •Patients with known brain metastases.
- •Grade 3 Cystitis infective and non-infective.
- •Severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with the study participation or the study treatment administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for enrollment in this study.
- •More than 1 prior treatment with PSMA-targeted radioconjugate.
- •Previous treatment with Actinium-225, Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, or hemi-body irradiation or any other radionuclide therapy except \[177Lu\]Lu-PSMA-617 and Radium-
- •Radium-223 within 6 months prior to the first study treatment administration.
- •Prior radioconjugate treatment within 6 weeks prior to first study treatment administration. Adverse events from prior radioconjugate treatment must be resolved or reduced to grade 1 prior to the first study treatment administration.
- •More than 6 administrations of previous radioconjugate treatment.
- •Any systemic anti-cancer therapy (e.g., chemotherapy, immunotherapy or biological therapy \[including monoclonal antibodies\]) within 6 weeks prior to the first study treatment administration. Patients on a stable bisphosphonate or denosumab regimen for 30 days prior to first study treatment administration are eligible.
- •Evidence of superscan in the baseline bone scan.
Arms & Interventions
[225Ac]Ac-FL-020
Treatment with \[225Ac\]Ac-FL-020 administered intravenously. 10 patients will also receive \[111In\]In-FL-020 for dosimetry purposes.
Intervention: [225Ac]Ac-FL-020
[225Ac]Ac-FL-020
Treatment with \[225Ac\]Ac-FL-020 administered intravenously. 10 patients will also receive \[111In\]In-FL-020 for dosimetry purposes.
Intervention: Blood samples for PK
[225Ac]Ac-FL-020
Treatment with \[225Ac\]Ac-FL-020 administered intravenously. 10 patients will also receive \[111In\]In-FL-020 for dosimetry purposes.
Intervention: [111In]In-FL-020
[225Ac]Ac-FL-020
Treatment with \[225Ac\]Ac-FL-020 administered intravenously. 10 patients will also receive \[111In\]In-FL-020 for dosimetry purposes.
Intervention: Blood and urine samples collection
[225Ac]Ac-FL-020
Treatment with \[225Ac\]Ac-FL-020 administered intravenously. 10 patients will also receive \[111In\]In-FL-020 for dosimetry purposes.
Intervention: SPECT/CT images
Outcomes
Primary Outcomes
Dose escalation: Incidence of Dose-Limiting Toxicities (DLTs).
Time Frame: 28 days after the first injection of [225Ac]Ac-FL-020
RP2D
Dose escalation and dose expansion: Type, frequency and severity of adverse events (AEs) and serious adverse events (SAEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time Frame: From ICF signature and up to 42 days after the last dose of study treatment for all AE and SAE. Then only the AE/SAE suspected to be related to the study treatment will be reported.
Secondary Outcomes
- Dose escalation and dose expansion: Absorbed doses(During one week following the injection of [111In]In-FL-020)
- Area Under the Plasma concentration versus time curve(During one week following the first injection of [225Ac]Ac-FL-020)
- Peak Plasma Concentration (Cmax)(During one week following the first injection of [225Ac]Ac-FL-020)
- Progression Free Survival(2 years)
- Overall Survival(2 years)
- Overall response rate(2 years)
- Disease Control Rate(2 years)
- Best Overall response(2 years)