A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck

Study Overview
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Brief Summary
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The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 in patients with recurrent or metastatic squamous cell carcinoma of head and neck.

Detailed Description
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The study consists of two stages. In Part A, approximately 22 patients will be enrolled to evaluate the safety and preliminarily efficacy of MRG003. Based on the initial safety and efficacy data obtained from the Part A, the study design of second stage Part B single-arm study either will be continued or the trail will be terminated. If the Part A data support the continuation of the study, in the second stage, approximately an additional 98 patients will be enrolled to further evaluate the efficacy and safety of MRG003.

Official Title
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An Open-Label, Single Arm, Multi-Center Phase II Clinical Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck.

Conditions
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Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck

Intervention / Treatment
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* Drug: MRG003


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing to sign the ICF and follow the requirements specified in the protocol. Age: ≥18 years, both genders. Expected survival time≥3 months. Patients with histologically confirmed unresectable recurrent or metastatic squamous cell carcinoma of head and neck. Failed in the prior platinum and/or anti-PD-1 treatment. Patients must have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1). ECOG performance score 0 or 1. Organ functions and coagulation function must meet the basic requirements. No severe cardiac dysfunction with left ventricular ejection fraction (LVEF) ≥ 50%. Serum or urine pregnancy test negative within 7 days before the first dose of investigational drug. 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 4 or more systemic anti-tumor therapies for the recurrent or metastatic squamous cell carcinoma of head and neck. Expected surgery or any other form of systemic or local anti-tumor therapy. History of systemic chemotherapy within 3 weeks before the first administration of the investigational drug, targeted small molecule therapy within 2 weeks or 5 half-life periods before the first administration (whichever is shorter), antitumor biological therapy or immunotherapy within 4 weeks before the first administration, or major surgery. Known active CNS metastasis and/or cancerous meningitis. Residual toxicity reactions caused by previous anti-tumor treatment or abnormal values of laboratory tests higher than grade 1 (CTCAE v5.0). Uncontrolled or poorly controlled heart disease. History of pulmonary embolism or deep vein thrombosis within 3 months before the first administration of the investigational drug. Known history of malignancy. Uncontrolled or poorly controlled hypertension. Patients with a history of active bleeding, coagulopathy, or receiving coumarin anticoagulation therapy. Known allergic reaction to any ingredients or excipients of MRG003. Known active hepatitis B or C. Complicated with severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosed as acquired immunodeficiency syndrome (AIDS); or uncontrolled autoimmune disease; or history of allogeneic tissue/organ transplantation, stem cell or bone marrow transplantation, or solid organ transplantation. Active bacterial, viral, fungal, rickettsia, or parasitic infections that require systemic anti-infective treatment. Vaccination of live virus vaccine within 30 days before the first administration of the study drug. Inactivated seasonal influenza vaccine or approved COVID-19 vaccine is allowed. Moderate to severe dyspnea at rest caused by advanced cancer or its complications, or severe primary lung disease, oxygen saturation < 93% in non-oxygen state, or history of any interstitial lung disease or interstitial lung disease (ILD) requiring oral or intravenous glucocorticoids or non-infectious pneumonia. Patients receiving immunology-based treatment for any reason. Uncontrolled pleural effusion, pericardial effusion or recurrent ascites. Potent CYP3A4 inhibitors or inducers are in use and cannot be discontinued. Women who are lactating or pregnant. Other conditions that in the clinical judgement of the investigator make the patient not suitable for participation in this study.

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: MRG003<br>On the first day of every 3 weeks, MRG003 will be administered via intravenous infusion at 2.0 mg/kg calculated based on the actual body weight | Drug: MRG003<br>* Administered intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Independent Review Committee (IRC) | ORR is defined as the proportions of patients with a complete response (CR) and partial response (PR). ORR will be assessed by Independent Review Committee (IRC) according to RECIST v1.1. | Baseline to study completion (up to 24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Investigator | ORR is defined as the proportions of patients 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 months) | 
| Progression Free Survival (PFS) and Progression Free Survival Rate (PFSR) | PFS is 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 months) | 
| Duration of Response (DoR) | DOR is 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 months) | 
| Disease Control Rate (DCR) | DCR is defined as the proportions of patients achieving CR, PR, and stable disease (SD) after treatment. | Baseline to study completion (up to 24 months) | 
| Overall Survival (OS) | OS is defined as the duration from the start of treatment to death of any cause. | Baseline to study completion (up to 24 months) | 
| Adverse Events (AEs) | Any reaction, side effect, or untoward event that occurs during the course of the clinical trial whether or not the event is considered related to the study drug. | Baseline to 45 days after the last dose of study treatment | 
| PK parameter for MRG003: Maximum Drug Concentration (Cmax) | Maximum observed plasma concentration. | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for MRG003: (AUClast) | Area under the curve up to the last validated measurable plasma concentration | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for total antibody (TAb): Cmax | Maximum observed plasma concentration. | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for TAb: AUClast | Area under the curve up to the last validated measurable plasma concentration | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for Monomethyl Auristatin E (MMAE): Cmax | Maximum observed plasma concentration. | Baseline to 30 days after the last dose of study treatment | 
| PK parameter for MMAE: AUClast | Area under the curve up to the last validated measurable plasma concentration | Baseline to 30 days after the last dose of study treatment | 
| Incidence of anti-drug antibody (ADA) | The proportion of patients with positive ADA immunogenicity results. | Baseline to 30 days after the last dose of study treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRG003, Antibody Drug Conjugate (ADC), Squamous Cell Carcinoma of Head and Neck, EGFR