A Study of MHB088C Combined With MHB039A in Patients With Advanced Malignant Solid Tumors

Официальное название

An Open-label Phase I/II Clinical Study of MHB088C for Injection Combined With MHB039A for Injection in Patients With Advanced Malignant Solid Tumors

Обзор

This is a first-in-human, open-label, multicenter Phase I/II study of MHB088C combined with MHB039A in patients with advanced malignant solid tumors. The study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MHB088C and MHB039A combination therapy.

Подробное описание

This first-in-human clinical trial of MHB088C and MHB039A combination therapy comprises two parts: a dose escalation phase and indication expansion phase. The dose escalation phase is an open-label, multicenter study including dose escalation and PK expansion cohorts. The primary objectives are to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of MHB088C combined with MHB039A in patients with advanced solid tumors, and to determine the maximum tolerated dose (MTD). Additional patients may be enrolled in the PK expansion part at dose levels that have completed DLT (dose-limiting toxicity) evaluation.

Based on the safety, PK, and preliminary efficacy data from the completed DLT-evaluated dose levels, the sponsor will initiate the indication expansion phase to further evaluate the safety and efficacy of MHB088C and MHB039A combination therapy in patients with specific types of advanced solid tumors.

Вмешательства

• Препарат MHB088C for Injection
  Intravenous administration
• Препарат MHB039A for Injection
  Intravenous administration

Первичные конечные точки

• (Dose-Escalation Stage): Dose-Limiting Toxicity (DLT) and Maximum tolerated dose (MTD) for MHB088C and MHB039A combination therapy [Срок оценки: Up to day 21 from the first dose for Q3W administration, or up to day 28 from the first dose for Q2W administration.]
• (Dose-Expansion Stage): Objective tumor response (ORR) determined by investigators according to RECIST v1.1 [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]

Вторичные конечные точки (7)

• Incidence and severity of adverse events (AEs) [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years.]
• Pharmacokinetic (PK) parameters of total antibody, ADC, and free toxin at various time points [Срок оценки: From pre-dose to 22 days after the first dose]
• Pharmacokinetic (PK) parameters of total antibody, ADC, and free toxin at various time points [Срок оценки: From pre-dose to 22 days after the first dose]
• Duration of response (DOR) determined by investigators according to RECIST v1.1 [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]
• Disease control rate (DCR) determined by investigators according to RECIST v1.1 [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]
• Progression-free survival (PFS) determined by investigators according to RECIST v1.1 [Срок оценки: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years]
• Overall survival (OS) [Срок оценки: Baseline up until death up to approximately 5 years]

Критерии участия

Критерии включения

• Voluntarily agrees to participate in the study and signs the informed consent form.
• Age ≥ 18 years, no restriction on gender.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Estimated life expectancy ≥ 3 months.
• For the dose escalation stage: Histologically or cytologically confirmed advanced solid tumors that are refractory to standard therapy, intolerant to standard therapy, or have no standard treatment options.
• For the dose expansion stage: Histologically or cytologically confirmed locally advanced or metastatic advanced solid tumors, not suitable for radical surgery and/or radical concurrent/sequential radiotherapy and chemotherapy.
• At least one measurable lesion per RECIST v1.1 criteria.
• Adequate bone marrow reserve and organ function.
• Eligible participants of childbearing potential (males and females) must agree to take highly reliable contraceptive measures with their partners during the study and within at least 12 weeks after the last dose.

Критерии исключения

• History of ≥2 primary malignancies within 5 years prior to informed consent.
• Received chemotherapy within 3 weeks, radiotherapy within 4 weeks, or biologic, endocrine, or immunotherapy within 4 weeks before dosing.
• Medication of other unmarketed investigational drugs or therapies within 4 weeks before dosing.
• Brain metastases, leptomeningeal disease, brainstem metastases, or spinal cord compression.
• Underwent major organ surgery (excluding biopsy) or significant trauma within 4 weeks before the first dose of investigational drug or requiring elective surgery during the study.
• Previous or concurrent gastrointestinal perforation, surgical procedures and wound healing complications, as well as bleeding events.
• Received intravenous thrombolysis treatment within 2 weeks, except for preventive anticoagulation and antiplatelet therapy.
• Vaccinated within 4 weeks before dosing.
• Treated with systemic corticosteroids within 14 days before dosing.
• Severe lung disease affecting pulmonary function.
• Active systemic infection requiring treatment within 7 days before dosing.
• Uncontrolled third-space effusion.
• Serious cardiovascular or cerebrovascular diseases.
• Known hypersensitivity or delayed allergic reaction to the investigational product or its components.
• Drug abuse or other medical/psychiatric condition that may interfere with study participation or results.
• Known alcohol or drug dependence.
• Pregnant or breastfeeding women, or individuals planning to conceive.

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 · 1 центр

• Ethics Committee of Shanghai East Hospital — Шанхай

Идентификаторы

NCT: NCT07126665 · MHB088C-E-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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