A Study to Assess Safety and Efficacy of PRL3-Zumab in Patients With Solid Tumors

Study Overview
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Brief Summary
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This is a multi-center, Phase 2, open-label, single dose level study of PRL3-zumab monotherapy in patients with unresectable or metastatic solid tumor.

Detailed Description
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The study consists of a Screening Period (Day - 14 to Day -1), a Treatment Period during which visits will occur every 2 weeks, an End of Treatment visit within 14 days of the decision to discontinue treatment for any reason, and a Safety Follow-up visit at 14 ± 4 days after the last dose of study treatment. PRL3-zumab will be administered by intravenous (IV) infusion till patient meets any of the discontinuation criteria (progressive disease, clinically or per RECIST v1.1 and iRECIST, intolerable toxicity or withdrawal of consent). One cycle of treatment will be 4 weeks (2 infusions, 12 days ±2 days apart).

Official Title
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An Open Label, Multicenter, Safety and Efficacy Phase 2 Study of PRL3-Zumab in Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: PRL3-zumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with unresectable or metastatic solid tumors willing to provide signed informed consent. Histopathological diagnosis and metastatic status cancer at study entry. Must have received at least 1 prior line of systemic therapy for metastatic disease but no more than 3 prior lines of treatment for metastatic disease. Life expectancy of more than 6 months. Eastern Cooperative Oncology Group (ECOG) performance status (PS) score or less than 2. Adequate organ and hematological function. Measurable disease by RECIST v1.1 and iRECIST. Exclusion Criteria: Patient has known untreated or symptomatic central nervous system metastasis. Patient is receiving systemic glucocorticoids or other immunosuppressive treatments for autoimmune disease or any other medical condition. Patient has experienced a severe hypersensitivity reaction to another monoclonal antibody. Patient has received treatment with any systemic anti-cancer therapies within 3 weeks prior to starting study treatment. Patient has undergone radiotherapy ≤ 4 weeks prior to starting study treatment. Patient has received > 3 lines of prior systemic chemotherapy for metastatic disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRL3-zumab<br>All patients will receive PRL3-zumab until clinical progression per RECIST v1.1 and iRECIST criteria, or unacceptable toxicity, or withdraws consent. | Biological: PRL3-zumab<br>* Starting dose of 6 mg/kg will be administered as IV infusion over 60 minutes every 2 weeks (±2 days)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | PFS is defined as the time from the initiation of study treatment to the date of disease progression as per RECIST v1.1 and iRECIST criteria. | From first dose of study drug until disease progression or end of treatment, whichever comes first | 
| Objective response rate (ORR) | ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) as per RECIST v1.1 and iRECIST criteria from time of initiation of study treatment. | From first dose of study drug until disease progression or end of treatment, whichever comes first | 
| Clinical benefit rate (CBR) | CBR is defined as the percentage of patients with CR, PR, or stable disease (SD) as per RECIST v1.1 and iRECIST criteria based on Investigator's assessment. | From first dose of study drug until disease progression or end of treatment, whichever comes first | 
| Overall survival (OS) | OS is defined as the time from the initiation of study treatment to death from any cause. | From first dose of study drug until disease progression or end of treatment, whichever comes first | 
| Duration of response | Duration of response is defined as the time from the initial documented response (CR or PR) to the first documented sign of disease progression as per RECIST v1.1 and iRECIST criteria or death. | From first dose of study drug until disease progression or end of treatment, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma PRL3-zumab concentration (Cmax) | To assess pharmacokinetics (PK) after single and multiple dose administration of PRL3-zumab. | Pre-dose and during first dose of C1, pre dose C1D15, C2D1, C2D15, C3D1, and pre dose and during the second dose of C3, pre-dose C4D1, C5D1, C6D1 and at end of treatment (up to approximately 6 months). Duration of 1 cycle is 4 weeks. C = Cycle, D = Day. | 
| Time of Cmax (tmax) | To assess PK after single and multiple dose administration of PRL3-zumab. | Pre-dose and during first dose of C1, pre dose C1D15, C2D1, C2D15, C3D1, and pre dose and during the second dose of C3, pre-dose C4D1, C5D1, C6D1 and at end of treatment (up to approximately 6 months). Duration of 1 cycle is 4 weeks. C = Cycle, D = Day. | 
| Area under the concentration time curve from pre-dose (AUCinf) | To assess PK after single and multiple dose administration of PRL3-zumab. | Pre-dose and during first dose of C1, pre dose C1D15, C2D1, C2D15, C3D1, and pre dose and during the second dose of C3, pre-dose C4D1, C5D1, C6D1 and at end of treatment (up to approximately 6 months). Duration of 1 cycle is 4 weeks. C = Cycle, D = Day. | 
| Terminal elimination half life (t½) | To assess PK after single and multiple dose administration of PRL3-zumab. | Pre-dose and during first dose of C1, pre dose C1D15, C2D1, C2D15, C3D1, and pre dose and during the second dose of C3, pre-dose C4D1, C5D1, C6D1 and at end of treatment (up to approximately 6 months). Duration of 1 cycle is 4 weeks. C = Cycle, D = Day. | 
| Number of patients with adverse events and serious adverse events | To assess safety of PRL3-zumab in patients with unresectable or metastatic solid tumors. | From first dose of study drug until disease progression or end of treatment, whichever comes first | 
| European Quality-5D (EQ-5D) | The system comprises 5 questions, 1 for each of 5 domains: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Each is rated according to 3 response levels (no problems, some problems, or extreme problems). | From first dose of study drug until disease progression or end of treatment, whichever comes first | 
| European Organization for Research and Treatment of Cancer-quality of life quantionnaire-C30 (EORTC-QLQ-C30) | Health-related quality of life is measured by EORTC-QLQ-C30, a 30 item questionnaire. This scale consists of functioning scales and symptom scales. For functioning scales higher scores suggest better functioning; for symptom scales higher scores suggest higher symptom burden. | From first dose of study drug until disease progression or end of treatment, whichever comes first | 
| Eastern Cooperative Oncology Group Performance Status (ECOG PS) | To assess safety of PRL3-zumab in patients with unresectable or metastatic solid tumors. | From first dose of study drug until disease progression or end of treatment, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PRL-3, Tumor, Efficacy, Safety, Pharmacokinetics