Clinical trial NCT04868162: A Study to Evaluate the Efficacy and Safety of MRG003 in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck
Keywords: MRG003
Antibody Drug Conjugate (ADC)
Squamous Cell Carcinoma of Head and Neck
EGFR
Lead sponsor: Shanghai Miracogen Inc.
Sponsor class: INDUSTRY
First posted: 2021-04-30
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) by Independent Review Committee (IRC)
timeFrame: Baseline to study completion (up to 24 months)
Secondary outcomes:
measure: Objective Response Rate (ORR) by Investigator
timeFrame: Baseline to study completion (up to 24 months)
measure: Progression Free Survival (PFS) and Progression Free Survival Rate (PFSR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Duration of Response (DoR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Disease Control Rate (DCR)
timeFrame: Baseline to study completion (up to 24 months)
measure: Overall Survival (OS)
timeFrame: Baseline to study completion (up to 24 months)
measure: Adverse Events (AEs)
timeFrame: Baseline to 45 days after the last dose of study treatment
measure: PK parameter for MRG003: Maximum Drug Concentration (Cmax)
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for MRG003: (AUClast)
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for total antibody (TAb): Cmax
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for TAb: AUClast
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for Monomethyl Auristatin E (MMAE): Cmax
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: PK parameter for MMAE: AUClast
timeFrame: Baseline to 30 days after the last dose of study treatment
measure: Incidence of anti-drug antibody (ADA)
timeFrame: Baseline to 30 days after the last dose of study treatment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
Study officials:
affiliation: Shanghai East Hospital
name: Ye Guo, Doctor
role: PRINCIPAL_INVESTIGATOR
References: