A Study of FZ-AD004 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This study is one single group of participants with advanced solid tumors. It is the first time the drug has been used in humans. There will be two parts including Dose Escalation and Dose Expansion to evaluate the safety, tolerability, pharmacokinetics, and clinical activity of FZ-AD004.

Detailed Description
-----------------
This is a first-in-human (FIH), Phase 1, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of FZ-AD004 in patients with advanced/metastatic solid tumors. FZ-AD004 is administered via intravenous infusion using an accelerated titration method followed by a conventional 3 + 3 study design to identify the maximum tolerated dose (MTD) and dose-limiting toxicities（DLT）during cycle 1. In addition, the maximum-tolerated dose and recommended Phase II dose for FZ-AD004 will be determined.

Official Title
-----------------
A PhaseⅠStudy to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of FZ-AD004 in Patients With Advanced Solid Tumors

Conditions
-----------------
Advanced and Metastatic Solid Tumor

Intervention / Treatment
-----------------
* Drug: FZ-AD004


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients able to give written informed consent; Age ≥ 18 and ≤ 75 years old, male or female; Patients have histological or cytological diagnosis with advanced solid tumors. Have measurable lesions defined in RECIST v. 1.1; Expected survival ≥ 12 weeks; Eastern Cancer Cooperative Group (ECOG) performance status 0-1; Patients of child bearing potential must agree to take contraception during the study and for 6 months after the last day of treatment. Exclusion Criteria: Have had other malignant tumors in the past 5 years; Have CNS (central nervous system) metastasis with clinical symptoms; Had undergone major surgery or severe trauma within 4 weeks prior to the first dose; Had undergone systemic high-dose steroids within 2 weeks of initiation of study treatment; Have history of psychotropic drug abuse, alcohol or drug abuse； Women who are pregnant or lactating； Other circumstances that is deemed not appropriate for the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: FZ-AD004<br>Participants enrolled in the dose escalation part or dose expansion part | Drug: FZ-AD004<br>* Dose Escalation：Subjects will receive an intravenous infusion of FZ-AD004 in a dose escalation until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study. Dose Expansion：Subject will receive a single dose of FZ-AD004 at 1-2 dose level on Day1 of each cycles.<br>* Other names: FZ-AD004-Antibody-drug Conjugate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The dose limiting toxicity ( DLT) | To determine the dose limiting toxicities (DLTs) of FZ-AD004. | 21 Days (first cycle) | 
| Maximum Tolerable Dose (MTD) | To determine the maximum tolerated dose (MTD) and/or recommended doses for expansion (RDEs). RDEs will not exceed MTD. | 21 Days (first cycle) | 
| Adverse Events | To check the numbers of AEs happened during the course of trial. | Screening up to study completion | 
| Objective Response Rate (ORR) according to RECIST 1.1 | To evaluate the objective response rate (ORR) [Complete Response (CR) + Partial Response (PR)] of FZ-AD004 when administered intravenously (IV) as monotherapy at the RDEs to patients with metastatic or locally advanced unresectable tumors. | From subject randomization up to 60 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival(PFS) according to RECIST 1.1 | Progression-free survival (PFS) was defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first. | From subject randomization up to 60 months. | 
| Duration of Response(DOR) according to RECIST 1.1 | Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). | From subject randomization up to 60 months | 
| Overall Survival (OS) according to RECIST 1.1 | Overall survival was defined as the time from the date of the first dose start date to the date of death due to any cause. | From subject randomization up to 60 months. | 
| Terminal elimination half-life (t1/2) of Total Antibody, Free DXd and FZ-AD004 | To check how much time Total Antibody, Free DXd and FZ-AD004 will take to eliminate half of it's concentration from participants. | Up to 17 weeks | 
| Maximum observed plasma concentration (Cmax) of Total Antibody, Free DXd and FZ-AD004 | o check what will be the maximum concentration participants will obtained of Total Antibody, Free DXd and FZ-AD004 in their blood plasma. | Up to 17 weeks | 
| Area under the concentration-time curve (AUC 0-∞) from time 0 to infinity of Total Antibody, Free DXd and FZ-AD004 | To check the drug profile for absorption, distribution, metabolism and excretion for Total Antibody, Free DXd and FZ-AD004 in participants blood plasma | Up to 17 weeks | 
| Time to Cmax (Tmax) of Total Antibody, Free DXd and FZ-AD004 | To check what time will it take to reach the maximum contraction of Total Antibody, Free DXd and FZ-AD004 in study participants | Up to 17 weeks | 
| Number of subjects who develop detectable anti-drug antibodies (ADAs) | To check the Anti Drug Antibody develops in participants against the FZ-AD004 through blood sample | From subject randomization up to 60 months. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced and Metastatic Solid Tumor