Phase 1/2 Clinical Study of Lutetium Lu 177 JH020002 Injection in Patients With Advanced Prostate Cancer

Study Overview
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Brief Summary
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The study is being conducted to evaluate the safety, tolerability, pharmacokinetics, radiation dosimetry, and preliminary efficacy of Lutetium Lu 177 JH020002 Injection in adult patients with advanced prostate cancer.

Official Title
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Phase 1/2 Clinical Study to Evaluate the Safety, Tolerability, Radiation Dosimetry and Preliminary Efficacy of Lutetium Lu 177 JH020002 Injection in Patients With Advanced Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Lutetium Lu 177 JH020002 Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects are required to get informed consent prior to the trial and sign a written informed consent form voluntarily. Male, age ≥18 years. ECOG score 0 - 2. Must have a life expectancy >6 months. Histologically and/or cytologically confirmed adenocarcinoma of the prostate (except for those with neuroendocrine or small cell prostate cancer clinical features). Participants must have a castrate level of serum/plasma testosterone (< 50 ng/dl, or < 1.7nmol/L). Exclusion Criteria: Diagnosed with other malignancies, apart from: adequately treated skin basal cell carcinoma or superficial bladder cancers from which the patient has been disease-free for more than 3 years as confirmed by a physician. Participants with a history of central nervous system (CNS) metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223 or hemi-body irradiation <6 months prior to date of first administration of investigational drug. Previous PSMA-targeted radioligand therapy. Previous radiotherapy for prostate cancer within 4 weeks prior to date of first administration of investigational drug. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy, poly adenosine diphosphate-ribosyl polymerase inhibitors (PARPi) or biological therapy within 4 weeks prior to date of first administration of investigational drug. Must not take part in other investigational therapies within 4 weeks prior to date of first administration of investigational drug. History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lutetium Lu 177 JH020002 Injection<br> | Drug: Lutetium Lu 177 JH020002 Injection<br>* Patients will receive Lutetium Lu 177 JH020002 Injection every 6 weeks for a maximum of 6 doses. Doses range between 1.85 and 8.88 GBq (50-240 mCi)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) (Phase 1) | Incidence of adverse events, serious adverse events, and clinical laboratory abnormalities defined as dose-limiting toxicities (DLTs). | Up to 2 years follow up | 
| Maximum Tolerated Dose (MTD) (Phase 1) | The maximum tolerated dose is among the explored dose levels. | Up to 2 years follow up | 
| Recommended Phase 2 Dose (RP2D) (Phase 1) | To identify the expansion phase dose of Lutetium Lu 177 JH020002 Injection. | Up to 2 years follow up | 
| Objective Response Rate (ORR) (Phase 2) | Proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR was based on the Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria response for patients with measurable disease at baseline. | Up to 2 years follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation Dosimetry | Absorbed dose estimated in organs and tumor lesions. | Up to 2 years follow up | 
| Maximum plasma concentration (Cmax) | Pharmacokinetics (PK) characterization of Lutetium Lu 177 JH020002. | Up to 2 years follow up | 
| Time to maximum plasma concentration (Tmax) | Pharmacokinetics (PK) characterization of Lutetium Lu 177 JH020002. | Up to 2 years follow up | 
| Terminal elimination half-life (t1/2) | Pharmacokinetics (PK) characterization of Lutetium Lu 177 JH020002. | Up to 2 years follow up | 
| Total systemic clearance (CL) | Pharmacokinetics (PK) characterization of Lutetium Lu 177 JH020002. | Up to 2 years follow up | 
| Area under the plasma concentration-time curve from time zero to the last measurable concentration (AUC0-t) | Pharmacokinetics (PK) characterization of Lutetium Lu 177 JH020002. | Up to 2 years follow up | 
| Area under the plasma concentration-time curve from time zero extrapolated to infinite time (AUC0-inf) | Pharmacokinetics (PK) characterization of Lutetium Lu 177 JH020002. | Up to 2 years follow up | 
| Volume of distribution (Vz) during the terminal phase following intravenous elimination | Pharmacokinetics (PK) characterization of Lutetium Lu 177 JH020002. | Up to 2 years follow up | 
| Radiographic Progression-free Survival (rPFS) | Radiographic progression free survival (rPFS) is defined as the time of radiographic progression by Prostate Cancer Working Group 3 (PCWG3)-modified RECIST V1.1. | Up to 3 years follow up | 
| Disease control Rate (DCR) | Disease control rate (DCR) is defined as the proportion of participants with best overall response of complete response or partial response or Stable disease in soft tissue according to PCWG3 modified RECIST 1.1. | Up to 3 years follow up | 
| Duration of Response (DoR) | Duration of response (DOR) is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue as per BIRC and according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause. | Up to 3 years follow up | 
| Time to First Subsequent Therapy (TFST) | Time to First Subsequent Therapy (TFST) is defined as the time from the date of first administration of investigational drug to the date of the first subsequent therapy of the prostate cancer. | Up to 3 years follow up | 
| Overall Survival (OS) | Overall survival (OS) is defined as the time from the date of first administration of investigational drug to the date of death due to any cause. | Up to 3 years follow up | 
| PSA50 Response Rate | PSA response rate is the proportion of PSA responders, defined as a participant who has achieved PSA decrease of >= 50% from baseline that is confirmed by a second consecutive PSA measurement >= 4 weeks later. Determination of response status will be based on PCWG3 recommendations. | Up to 3 years follow up | 
| Time to Symptomatic Skeletal Event (TTSSE) | Time to a first symptomatic skeletal event (TTSSE) is defined as date of first administration of investigational drug to the date of first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurs first. | Up to 3 years follow up | 
| Incidence and severity of Adverse Events (AEs) and Serious Adverse Event (SAEs) | Analysis of frequencies and severity for Adverse Events (AEs) and Serious Adverse Event (SAEs), through the monitoring of relevant clinical and laboratory safety parameters. | Up to 3 years follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer