A Study of MRG007 (ARR-217) in Patients With Advanced Solid Tumors

Официальное название

An Open-Label, Multi-Center, Dose Escalation, Confirmation, and Expansion Phase I Clinical Study to Evaluate the Safety, Tolerability, Efficacy, and Pharmacokinetics of MRG007 (ARR-217) in Participants With Unresectable Locally Advanced or Metastatic Solid Tumors

Обзор

This is an open-label, multi-center, phase I study to evaluate the safety, tolerability, efficacy, and pharmacokinetics of MRG007 (ARR-217) in patients with unresectable locally advanced or metastatic solid tumors.

Вмешательства

• Препарат MRG007
  MRG007 will be administrated as specified in the protocol.
• Препарат MRG007 and Bevacizumab
  MRG007 will be administered as specified in the protocol

Первичные конечные точки

• Dose Limiting Toxicity (DLT) - Phase Ia [Срок оценки: Baseline to Day 21 of the first treatment cycle]
• Serious Adverse Events (SAEs) [Срок оценки: Baseline to 30 days after the last dose of study treatment]
• Treatment-Emergent Adverse Event (TEAE) [Срок оценки: Baseline to 30 days after the last dose of study treatment]
• Treatment-Related Adverse Event [Срок оценки: Baseline to 30 days after the last dose of study treatment]
• Objective Response Rate (ORR) as assessed by investigator - Phase Ib [Срок оценки: Baseline to study completion (up to 24 months)]

Вторичные конечные точки (11)

• Objective Response Rate (ORR) - Phase Ia [Срок оценки: Baseline to study completion (up to 24 months)]
• 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)]
• Incidence of anti-drug antibody (ADA) [Срок оценки: Baseline to 30 days after the last dose.]
• Incidence of neutralizing antibody (NAb) [Срок оценки: Baseline to 30 days after the last dose.]
• 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]
• AUC0-t [Срок оценки: Baseline to 30 days after the last dose of study treatment]
• QTc interval [Срок оценки: Baseline to 30 days after the last dose of study treatment]

Критерии участия

• Willing to sign the informed consent form and follow the requirements specified in the protocol.
• Life expectancy ≥ 3 months.
• Tumor specimen available for CDH17 testing, or agree to biopsy at baseline.
• Patients with histologically and cytologically confirmed advanced or metastatic solid tumor who have failed or intolerant to standard therapy, or without alternative standard therapy.
• Patients must have at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1).
• The score of ECOG for performance status is 0 or 1.
• Organ functions and coagulation function must meet the basic requirements.
• Patients with childbearing potential must use effective contraception during the treatment and for 6 months after the last dose of treatment.

Критерии исключения

• Patients with more than one cancer.
• Received CDH17-targeting anti-tumor therapy; received other investigational product, systemic corticosteroids or surgery for major organs within 4 weeks prior to the first dose; received anti-tumor therapy within 3 weeks or within 5 half-lives prior to the first dose, whichever is shorter; received radiotherapy within 2 weeks prior to the first dose; received strong CYP3A4 inducers or inhibitors within 2 weeks prior to the first dose or 5 half-lives, whichever is longer; investigational therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to the first dose.
• ≥Grade 2 toxic reaction or abnormal value of laboratory test caused by previous anti-tumor treatment
• Symptomatic Central nervous system and/or meninges metastasis.
• History of severe cardiovascular diseases
• Cerebrovascular accident, pulmonary embolism, or deep venous thrombosis within 3 months prior to the first dose, implantable venous infusion port or catheter-related thrombosis, or superficial venous thrombosis
• History of previous or combined interstitial pneumonia, current interstitial pneumonia, or suspected interstitial pneumonia that cannot be ruled out through imaging during screening, severe chronic obstructive pulmonary disease with respiratory failure, severe pulmonary dysfunction, symptomatic bronchospasm, etc.
• Poorly controlled pleural, peritoneal, and pelvic effusion, or combined pericardial effusion
• Infection of active hepatitis B, active hepatitis C, or HIV
• Uncontrolled active bacterial, viral, fungal, rickettsial, or parasitic infections requiring intravenous anti-infection therapy within 2 weeks prior to the first study treatment
• Known allergic reactions to any component of MRG007, or known Grade≥3 allergic reactions to other prior anti-CDH17 (including investigational) or other monoclonal antibody.
• Other situations that are not suitable to participate a clinical trial per investigator's judgement
• Additional protocol-defined exclusion criteria apply

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 11 центров

• Peking University Cancer Hospital — Пекин
• Beijing Gobroad Hospital — Пекин
• Army Medical Center of PLA — Чунцин
• Sir Run Run Shaw Hospital, Zhejiang University School of Medicine — Zhejiang
• Harbin Medical University Cancer Hospital — Heilongjiang
• Henan Cancer Hospital — Чжэнчжоу
• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology — Ухань
• Hunan Cancer Hospital — Чанша
• … и ещё 3 центра

США · 10 центров

• ULCA — Los Angeles
• UCSF — San Francisco
• University of Colorado — Aurora
• Sarah Cannon Research Institute — Denver
• Sarah Cannon Research Institute — Sarasota
• Sarah Cannon Research Institute — Nashville
• MD Anderson Cancer Center — Houston
• NEXT Dallas — Irving
• … и ещё 2 центра

Идентификаторы

NCT: NCT07066657 · MRG007-001/ARR-217-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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