A Clinical Study of MHB034C for Injection in Participants With Advanced Solid Tumors
A Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of MHB034C for Injection in Participants With Advanced Solid Tumors
This study is an open-label, multicenter, first-in-human (FIH) Phase I/II clinical study to evaluate the safety, tolerability, pharmacokinetic (PK) profile, and preliminary efficacy of MHB034C in participants with advanced solid tumors.
研究概览
详细说明
The phaseI/II study consists of two stages: a dose escalation stage and a dose expansion stage. The primary objective of the Phase I dose escalation stage is to evaluate the safety and tolerability of MHB034C in participants with advanced solid tumors; the primary objective of the Phase II dose expansion stage is to evaluate the antitumor efficacy of MHB034C in selected participants with advanced solid tumors.
研究类型
注册 (估计的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名:VP of R&D
- 电话号码:+86 021-60898367
- 邮箱:jwshi@minghuipharma.com
学习地点
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Shanghai Municipality
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Shanghai、Shanghai Municipality、中国、201419
- Fudan University Shanghai Cancer Center
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接触:
- Ethics Committee
- 电话号码:85033 +86 021-64175590
- 邮箱:JJYIN555@163.com
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Participants voluntarily agree to participate in this study and sign the informed consent form.
- Aged ≥ 18 years, regardless of sex.
- ECOG Performance Status (PS) score of 0-1.
- Life expectancy of more than 3 months.
- Female participants of childbearing potential, and male participants whose partners are women of childbearing potential, must agree to use highly effective contraception with their partners; must refrain from donating gametes, from initiating gamete cryopreservation, and from retrieving or using their own previously cryopreserved gametes for conception. Female participants of childbearing potential must have a negative serum β-HCG pregnancy test within 7 days prior to the first use of the investigational medicinal product (IMP), and must not be lactating.
- Ability to understand the study requirements and willingness and ability to comply with the study and follow-up procedures.
- Participants enrolled in the Phase I dose escalation stage must have advanced solid tumors confirmed by histopathological or cytological examination, and must have progressed on or been intolerant to standard therapy, or have no standard treatment available.
- Participants enrolled in the Phase II dose expansion stage must have advanced solid tumors confirmed by histopathological or cytological examination, and must have progressed on or been intolerant to standard therapy, or have no standard treatment available.
- During the dose escalation stage, the investigator should make best efforts to obtain consent from participants to provide pre-treatment tumor tissue samples; during the dose expansion stage, participants must agree to provide pre-treatment tumor tissue samples, and if such samples cannot be provided, enrolment is permitted only with the sponsor's approval.
- At least one measurable tumor lesion according to the RECIST v1.1 criteria.
- Adequate bone marrow function.
- Adequate hepatic function.
- Adequate renal function.
- Adequate coagulation function.
- Adequate cardiac function.
Exclusion Criteria:
- Has had another primary malignancy within 3 years prior to signing the informed consent form, excluding early-stage malignancies that have been curatively treated.
- Has previously used or is currently using an antibody-drug conjugate (ADC) with a topoisomerase I inhibitor as the payload, with certain exceptions.
- Has previously received doxorubicin at a cumulative dose of > 360 mg/m² or an equivalent dose of a similar agent.
- Has received chemotherapy or endocrine therapy within 3 weeks, or radiotherapy, biological therapy, immunotherapy, or other anti-tumor therapy within 4 weeks, prior to the first dose of the investigational medicinal product .
- Has spinal cord compression, leptomeningeal metastasis, brainstem metastasis, or unstable brain metastasis.
- Adverse events from prior anti-tumor therapy have not resolved to ≤ Grade 1 as assessed by NCI-CTCAE v6.0.
- Has undergone major surgery on a major organ (excluding biopsy) or experienced significant trauma within 4 weeks prior to the first use of the IMP, or requires elective surgery during the study period, or currently has severe unhealed or dehiscent wounds, active and clinically significant ulcers, untreated fractures, or active unhealed stomatitis.
- Has received a live vaccine or live attenuated vaccine within 4 weeks prior to the first use of the IMP.
- Has received or requires systemic corticosteroids or other immunosuppressive therapy within 14 days prior to the first use of the IMP, excluding topical, ophthalmic, intra-articular, intranasal, and inhaled corticosteroid therapy, and short-term corticosteroid use for prophylaxis.
- Has moderate or severe pulmonary disease that significantly impairs pulmonary function.
- Has a history of interstitial lung disease/pneumonitis (ILD), currently has ILD, or suspected ILD that cannot be ruled out by imaging during screening.
- Has severe cardiovascular disease or high-risk factors.
- Has experienced an arterial/venous thrombotic event within 6 months prior to the first dose.
- Has a clinically evident or uncontrolled third-space fluid collection requiring repeated drainage.
- Currently has an active autoimmune disease, or has a history of active autoimmune disease requiring systemic immunosuppressive therapy within 2 years prior to the first use of the IMP.
- Has clinically significant corneal disease, or is currently using other medications that may cause corneal damage.
- Has an active infection requiring systemic therapy within 7 days prior to the first dose.
- Has clinically uncontrolled diabetes mellitus.
- Has active tuberculosis, or a history of tuberculosis infection that was not controlled after treatment, or is still receiving anti-tuberculosis therapy; or has active syphilis.
- Positive serological virology results: positive for HIV antibody; or positive for HBsAg or HBcAb with HBV-DNA ≥ 500 IU/mL; or positive for HCV antibody with positive HCV-RNA.
- Has experienced clinically significant bleeding symptoms or an obvious bleeding tendency within 1 month prior to the first dose.
- Has known hypersensitivity or delayed hypersensitivity to certain components or analogues of the IMP in this study.
- Has a history of severe neurological or psychiatric disorders, or a history of psychotropic substance abuse or drug abuse, or any other medical condition.
- Has known alcohol or drug dependence.
- Has insufficient compliance to participate in this clinical study in the investigator's judgment, or the investigator considers that the participant has a history of other serious systemic diseases or other conditions unsuitable for participation in this study.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的:MHB034C for Injection
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MHB034C for Injection |
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Phase I Dose Escalation Stage: Incidence of DLT
大体时间:At the end of Cycle 1 (each cycle is 21 days for Q3W administration and 28 days for Q2W administration)
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At the end of Cycle 1 (each cycle is 21 days for Q3W administration and 28 days for Q2W administration)
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Phase I Dose Escalation Stage: Incidence of Adverse events (AEs)
大体时间:from Day1 to 30 days after last dose
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from Day1 to 30 days after last dose
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Phase I Dose Escalation Stage: Incidence of Serious adverse events (SAEs)
大体时间:from Day1 to 30 days after last dose
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from Day1 to 30 days after last dose
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Phase I Dose Escalation Stage: MTD
大体时间:At the end of Cycle 1 (each cycle is 21 days for Q3W administration and 28 days for Q2W administration)
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At the end of Cycle 1 (each cycle is 21 days for Q3W administration and 28 days for Q2W administration)
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Phase I Dose Escalation Stage: RP2D
大体时间:from Day1 to 30 days after last dose
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from Day1 to 30 days after last dose
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Phase II Dose Expansion Stage: ORR as assessed by the investigator per RECIST v1.1.
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase II Dose Expansion Stage: DCR as assessed by the investigator per RECIST v1.1.
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase II Dose Expansion Stage: DoR as assessed by the investigator per RECIST v1.1.
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase II Dose Expansion Stage: PFS as assessed by the investigator per RECIST v1.1.
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase II Dose Expansion Stage: OS as assessed by the investigator per RECIST v1.1.
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase II Dose Expansion Stage: PFS rates at 6 and 12 months.
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase II Dose Expansion Stage: OS rates at 6 and 12 months.
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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次要结果测量
结果测量 |
大体时间 |
|---|---|
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Phase I Dose Escalation Stage: AUC0-t、AUC0-∞ of MHB034C
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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Phase I Dose Escalation Stage: Cmax of MHB034C
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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Phase I Dose Escalation Stage: Tmax of MHB034C
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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Phase I Dose Escalation Stage: CL of MHB034C
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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Phase I Dose Escalation Stage: t1/2 of MHB034C
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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Phase I Dose Escalation Stage: Vss of MHB034C
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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Phase I Dose Escalation Stage: Ctrough of MHB034C
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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Phase I Dose Escalation Stage and Phase II Dose Expansion Stage: Positivity rate of anti-MHB034C antibodies (ADA) and their possible neutralizing antibodies (NAb)
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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Phase I Dose Escalation Stage: ORR as assessed by the investigator per RECIST v1.1
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase I Dose Escalation Stage: DCR as assessed by the investigator per RECIST v1.1
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase I Dose Escalation Stage: DoR as assessed by the investigator per RECIST v1.1
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase I Dose Escalation Stage: PFS as assessed by the investigator per RECIST v1.1
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase I Dose Escalation Stage: OS as assessed by the investigator per RECIST v1.1
大体时间:One year after the last subject was enrolled in the group
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One year after the last subject was enrolled in the group
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Phase II Dose Expansion Stage: Incidence of AEs
大体时间:from Day1 to 30 days after last dose
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from Day1 to 30 days after last dose
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Phase II Dose Expansion Stage: Incidence of SAEs
大体时间:from Day1 to 30 days after last dose
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from Day1 to 30 days after last dose
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Phase II Dose Expansion Stage: Concentrations of total antibody, ADC, and free payload in participants after dosing
大体时间:through study completion, an average of 2 years
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through study completion, an average of 2 years
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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