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

Phase 2

• Conditions: Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck
• Interventions: Drug: MRG003

• Registration Number: NCT04868162
• Lead Sponsor: Shanghai Miracogen Inc.

Brief Summary

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

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.

Study Timeline

• Status Verified: 2021-04
• Study Start: 2021-04-23
• Study First Submitted: 2021-04-29
• Study First Submitted QC: 2021-04-29
• Last Update Submitted: 2021-04-29
• Study First Posted: 2021-04-30
• Last Update Posted: 2021-04-30
• Primary Completion: 2023-01
• Study Completion: 2023-09

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MRG003	MRG003	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

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) by Independent Review Committee (IRC)	Baseline to study completion (up to 24 months)	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.

Secondary Outcome Measures

Name	Time	Method
PK parameter for total antibody (TAb): Cmax	Baseline to 30 days after the last dose of study treatment	Maximum observed plasma concentration.
PK parameter for TAb: AUClast	Baseline to 30 days after the last dose of study treatment	Area under the curve up to the last validated measurable plasma concentration
Objective Response Rate (ORR) by Investigator	Baseline to study completion (up to 24 months)	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.
Progression Free Survival (PFS) and Progression Free Survival Rate (PFSR)	Baseline to study completion (up to 24 months)	PFS is defined as the duration from the start of treatment to the onset of tumor progression or death of any cause.
Duration of Response (DoR)	Baseline to study completion (up to 24 months)	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.
Disease Control Rate (DCR)	Baseline to study completion (up to 24 months)	DCR is defined as the proportions of patients achieving CR, PR, and stable disease (SD) after treatment.
Overall Survival (OS)	Baseline to study completion (up to 24 months)	OS is defined as the duration from the start of treatment to death of any cause.
Adverse Events (AEs)	Baseline to 45 days after the last dose of study treatment	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.
PK parameter for MRG003: Maximum Drug Concentration (Cmax)	Baseline to 30 days after the last dose of study treatment	Maximum observed plasma concentration.
PK parameter for MRG003: (AUClast)	Baseline to 30 days after the last dose of study treatment	Area under the curve up to the last validated measurable plasma concentration
PK parameter for Monomethyl Auristatin E (MMAE): Cmax	Baseline to 30 days after the last dose of study treatment	Maximum observed plasma concentration.
PK parameter for MMAE: AUClast	Baseline to 30 days after the last dose of study treatment	Area under the curve up to the last validated measurable plasma concentration
Incidence of anti-drug antibody (ADA)	Baseline to 30 days after the last dose of study treatment	The proportion of patients with positive ADA immunogenicity results.

Trial Locations

Locations (1)

Shanghai East Hospital; 🇨🇳 Shanghai, Shanghai, China