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

Официальное название

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.

Обзор

The objective of this study is to assess the safety, efficacy, pharmacokinetics, and immunogenicity of MRG003 and the combination of MRG003 and HX008 in patients with recurrent or metastatic squamous cell carcinoma of head and neck.

Подробное описание

The study consists of two stages. In Part A, approximately 60 patients will be enrolled to evaluate the safety and preliminarily efficacy of MRG003 at 2.0 and 2.3 mg/kg, to further explore the optimized dose. In Part B, 30 to 50 patients will be enrolled to evaluate the safety and preliminary efficacy of the combination of MRG003 and HX008.

Вмешательства

• Препарат MRG003
  On the first day of every 3 weeks, MRG003 will be administered via intravenous infusion at 2.0 mg/kg or 2.3 mg/kg.
• Препарат MRG003+HX008
  On the first day of every 3 weeks, MRG003 will be administered via intravenous infusion at 2.0 mg/kg or the recommended dose by SMC; and HX008 will be administered via intravenous infusion at 3.0 mg/kg

Первичные конечные точки

• Objective Response Rate (ORR) by Investigator per RECIST v1.1 [Срок оценки: Baseline to study completion (up to 24 months)]

Вторичные конечные точки (10)

• Disease Control Rate (DCR) [Срок оценки: Baseline to study completion (up to 24 months)]
• Duration of Response (DoR) [Срок оценки: Baseline to study completion (up to 24 months)]
• Progression Free Survival (PFS) as assessed by investigator [Срок оценки: Baseline to study completion (up to 24 months)]
• Overall Survival (OS) [Срок оценки: Baseline to study completion (up to 24 months)]
• Adverse Events (AEs) [Срок оценки: Baseline to 30 days after the last dose of study treatment]
• Serious Adverse Events (SAEs) [Срок оценки: Baseline to 45 days after the last dose of study treatment]
• Tmax [Срок оценки: Baseline to 30 days after the last dose of study treatment]
• Cmax [Срок оценки: Baseline to 30 days after the last dose of study treatment]
• AUClast [Срок оценки: Baseline to 30 days after the last dose of study treatment]
• Incidence of anti-drug antibody (ADA) [Срок оценки: Baseline to 30 days after the last dose of study treatment]

Критерии участия

Критерии включения

• Willing to sign the ICF and follow the requirements specified in the protocol.
• Expected survival time≥3 months.
• Patients with histologically confirmed unresectable recurrent or metastatic squamous cell carcinoma of head and neck.
• Failed prior platinum and/or anti-PD-1 treatment (Part A); failed or intolerant to at least one prior line of standard therapy (platinum-based regimen) (Part B)
• Patients must have at least one measurable lesion 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.
• 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.

Критерии исключения

• History of 4 or more systemic anti-tumor therapies for the recurrent or metastatic squamous cell carcinoma of head and neck.
• ≥Grade 2 peripheral neuropathy
• Prior anti-tumor therapy with MMAE/MMAF ADCs
• BMI≤17
• 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). Prior Grade 3 to 4 immune-related AE (irAE) or ≥Grade 2 heart-related irAE.
• 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.
• History of severe dermatosis.
• 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 investigational drugs.
• 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.
• History of previous or concurrent interstitial pneumonia, radiation pneumonitis, severe chronic obstructive pulmonary disease, severe pulmonary dysfunction, symptomatic bronchospasm, etc.
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai East Hospital — Шанхай

Идентификаторы

NCT: NCT04868162 · MRG003-004

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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