A Study of MRG003 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
The objective of this study is to assess the safety, efficacy, and pharmacokinetics of MRG003, as well as immunogenicity as defined by the incidence of anti-drug antibody (ADA) of MRG003 in patients with advanced solid tumors, including colorectal cancer, squamous cell carcinoma of head and neck, and nasopharyngeal carcinoma.

Detailed Description
-----------------
This study consists of two parts: Phase Ia dose escalation and Phase Ib dose expansion. The objective of Phase Ia is to determine MTD or RP2D, and Phase Ib is conducted to evaluate efficacy of MRG003 in patients with advanced colorectal cancer, squamous cell carcinoma of head and neck (SCCHN), and nasopharyngeal carcinoma.

Official Title
-----------------
An Open-Label, Dose-Finding, Phase I Study in Solid Tumors.

Conditions
-----------------
Advanced Solid Tumors

Intervention / Treatment
-----------------
* Drug: MRG003


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Willing to sign the ICF and follow the requirements specified in the protocol. Age: ≥18 years and ≤75 years, both genders Expected survival time≥12 weeks Phase Ia: Patients with histologically and cytologically confirmed advanced or metastatic solid tumor Phase Ib: Patients with histologically and cytologically confirmed EGFR-positive advanced or metastatic colorectal cancer, squamous cell carcinoma of head and neck, and nasopharyngeal carcinoma Subjects must have measurable lesions according to the response Evaluation Criteria In Solid Tumors（RECIST v1.1） ECOG performance score 0 or 1 Acceptable liver, renal, and hematologic function Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment Exclusion Criteria: History of hypersensitivity to any component of the investigational product Presence of central nervous system metastasis Prior history of other primary malignancies Known history of clinically significant hepatic diseases Evidence of active infection of human immunodeficiency virus (HIV) History of ophthalmic abnormalities Any severe or uncontrolled systemic disease judged by the investigator Patients with poorly controlled heart diseases Received radiotherapy, chemotherapy, biotherapy, immunotherapy or other anti-tumor drugs within 4 weeks prior to the first dose of study treatment Major surgery or surgical therapy for any cause within 4 weeks prior to the first dose of investigational drug Planned surgery or surgery is the best interest of patients as determined by investigator History of severe skin disease requiring interruption of previous EGFR targeted therapy; or chronic skin disease requiring oral or intravenous therapy Active concomitant diseases that might increase risks of toxicity Pregnancy, or breast feeding

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

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MRG003<br>Phase Ia: MRG003 will be administrated by an IV infusion of escalating doses (0.1, 0.3, 0.6, 1.0, 2.0, 2.5, 3.0 mg/kg) on Day 1 of every 3 weeks (Q3W); Phase Ib: MRG003 will be administrated by an IV infusion of MTD/RP2D. | Drug: MRG003<br>* Administered intravenously<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicity (DLT) - Phase Ia | DLT is assessed on Day 21 (Day 1 to 21) of the first dose administration. | First cycle (21 days) | 
| Objective Response Rate (ORR) - Phase Ib | ORR was defined as the proportions of subjects with a complete response (CR) and partial response (PR). ORR will be assessed by investigator according to RECIST v1.1. | Baseline to study completion (up to 24 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter for MRG003: Maximum Drug Concentration (Cmax) | Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics. | Baseline to study completion (up to 24 weeks) | 
| PK parameter for MRG003: Area Under the Curve Up to the Last Validated Measurable Plasma Concentration (AUClast) | AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statics. | Baseline to study completion (up to 24 weeks) | 
| PK parameter for total antibody (TAb): Cmax | Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics. | Baseline to study completion (up to 24 weeks) | 
| PK parameter for TAb: AUClast | AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statics. | Baseline to study completion (up to 24 weeks) | 
| PK parameter for Monomethyl Auristatin E (MMAE): Cmax | Cmax will be derived from the PK blood samples collected and will be summarized with descriptive statistics. | Baseline to study completion (up to 24 weeks) | 
| PK parameter for MMAE: AUClast | AUClast will be derived from the PK blood samples collected and will be summarized with descriptive statics. | Baseline to study completion (up to 24 weeks) | 
| Immunogenicity | Blood samples for anti-drug antibody (ADA) analysis will be collected each time according to the pre-defined timepoints. | Baseline to study completion (up to 24 weeks) | 
| Progression Free Survival (PFS) - Phase Ib only | PFS was defined as the duration from the start of treatment to the onset of tumor progression or death of any cause. | Baseline to study completion (up to 24 weeks) | 
| Duration of Response (DoR) - Phase Ib only | DOR was defined as the duration from the initial recording of objective disease response to the first onset of tumor progression, or death of any cause. | Baseline to study completion (up to 24 weeks) | 
| Overall Survival (OS) - Phase Ib only | OS was defined as the duration from the start of treatment to death of any cause. | Baseline to study completion (up to 24 weeks) | 
| Incidence of Adverse Events (AEs) | Incidence of AEs and serious adverse events (SAEs) will be assessed based on NCI-CTCAE v5.0 | Baseline to 30 days after the last dose of study treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MRG003, Antibody Drug Conjugate (ADC), Solid tumors