M6223 人体研究中的首次
2026年4月13日 更新者：EMD Serono Research & Development Institute, Inc.
I 期首次人体开放标签多剂量递增研究，旨在研究 M6223（一种 TIGIT 抑制剂）作为单一药物并与 Bintrafusp Alfa（抗PDL1/TGFß Trap）在患有转移性或局部晚期实体瘤的参与者中无法切除
本研究的主要目的是确定 M6223 作为单一药物（第 1A 部分）每 2 周（Q2W）的安全性、耐受性、药代动力学 (PK)、免疫原性和（如果观察到）最大耐受剂量 (MTD) ）方案和每 3 周一次（Q3W）方案以及 M6223 联合 bintrafusp alfa（第 1B 部分）用于转移性或局部晚期实体不可切除肿瘤参与者的 Q2W 方案。
研究概览
研究类型
介入性
注册 (实际的)
58
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 及以上 (成人、年长者)
接受健康志愿者
不
描述
纳入标准：
- 参与者患有经组织学或细胞学证实的局部晚期或晚期实体恶性肿瘤，这些肿瘤在标准治疗下难治或进展，并且没有其他已知的治疗方案可带来临床益处
- 筛选时东部合作肿瘤组表现状态 (ECOG PS) 为 0 至 1 的参与者
- 参与者有一个福尔马林固定的石蜡包埋块，其中包含肿瘤组织或至少 15 个（最好是 25 个）未染色的肿瘤载玻片，适用于基于免疫组织化学的蛋白质表达染色
- 预期寿命至少为 12 周的参与者
- 根据实体瘤反应评估标准 1.1 版 (RECIST 1.1) 患有可测量疾病的参与者
- 方案中定义的足够的血液学、肝和肾功能
- 其他协议定义的纳入标准可能适用
排除标准：
- 与先前治疗相关的持续毒性大于 (>) 1 级的参与者国家癌症研究所不良事件通用术语标准 (NCI-CTCAE) 版本 5.0，但是，脱发、感觉神经病变小于或等于 (<=) 2 级，或其他非免疫相关<= 2级不构成安全风险
- 先前进行过器官移植（包括同种异体干细胞移植）的参与者
- 先前与免疫检查点抑制剂相关的毒性大于等于 (>=) 3 NCI-CTCAE 5.0 版的参与者，除非在研究纳入前解决为 <= 1 级
- 当前有明显心脏传导异常的参与者，包括三次 12 导联心电图上的校正 QT 间期（QTcF，用 Fridericia 公式校正）延长 > 450 毫秒 (ms) 或心血管功能受损、室性心动过速、低钾血症或阵发性心房病史颤动、严重心律失常和猝死或长 QT 综合征家族史
- 血管、心血管或脑血管疾病史，如脑血管意外/中风（入组前不到 [<] 6 个月）、心肌梗塞（入组前 < 6 个月）、不稳定型心绞痛、充血性心力衰竭（纽约心脏关联分类等级 >= II）、深静脉血栓形成（入组前 < 3 个月）或肺血栓形成/栓塞（入组前 < 3 个月）
- 其他协议定义的排除标准可能适用
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：非随机化
- 介入模型：顺序分配
- 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：第 1A 部分：M6223 单一疗法
|
Participants received an intravenous (IV) infusion of M6223 at escalated doses every 2 weeks (Q2W) or every 3 weeks (Q3W) on Day 1 of each Cycle (Each cycle is of 14 days) according to the recommendation of the SMC(Safety Monitoring Committee) until the maximum tolerated dose(MTD) has been reached or confirmed disease progression.
Participants received an IV infusion of M6223 at escalated doses Q2W on Day 1 of each Cycle (Each cycle is of 21 days) according to the recommendation of the SMC until the MTD has been reached or confirmed disease progression.
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实验性的：第 1B 部分：M6223 + Bintrafusp alfa
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Participants received an intravenous (IV) infusion of M6223 at escalated doses every 2 weeks (Q2W) or every 3 weeks (Q3W) on Day 1 of each Cycle (Each cycle is of 14 days) according to the recommendation of the SMC(Safety Monitoring Committee) until the maximum tolerated dose(MTD) has been reached or confirmed disease progression.
Participants received an IV infusion of M6223 at escalated doses Q2W on Day 1 of each Cycle (Each cycle is of 21 days) according to the recommendation of the SMC until the MTD has been reached or confirmed disease progression.
Participants received an IV infusion of bintrafusp alfa Q2W on Day 1 of each Cycle (Cycle is 14 days) until confirmed disease progression.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Part 1A and 1B: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0
大体时间：Day 1 to Day 28
|
A DLT is defined as any Grade ≥ 3 non-hematologic AE or any Grade ≥ 4 hematologic AE according to the NCI-CTCAE, occurring during the DLT observation period (28 days from first administration of study intervention) that is not clearly related to the underlying disease or any previous or concomitant medication, concomitant disease or unrelated illness.
A DLT must be confirmed by the Safety Monitoring Committee.
DLT is considered if the following related AEs occur: • Grade ≥ 3 neutropenia with clinical signs/symptoms (e.g., febrile neutropenia).
• Grade ≥ 3 thrombocytopenia with medically concerning bleeding.
• A study intervention-related treatment-emergent AE that in the opinion of the SMC is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk.
• Grade ≥ 3 hematological AE with symptoms that require growth factor support or transfusion to prevent further damage to the participant.
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Day 1 to Day 28
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Part 1A and 1B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs
大体时间：Approximately 2 years 11 months
|
An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not.
A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important.
TEAEs were defined as events that started or worsened after first dose of study intervention until 30 days after last dose.
TEAEs included both serious and non-serious TEAEs.
Treatment-related TEAEs is defined as reasonably related to the study intervention.
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Approximately 2 years 11 months
|
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Part 1A and 1B: Number of Participants With TEAES With Severity of Grade Greater or Equal to 3 and TEAEs Leading to Deaths
大体时间：Approximately 2 years 11 months
|
An adverse event (AE) is any untoward medical occurrence in a participant temporally associated with the use of the study intervention, regardless of causality.
A serious AE results in death, is life-threatening, requires/prolongs hospitalization, causes disability/incapacity, leads to a congenital anomaly/birth defect, or is otherwise medically significant.
Treatment-emergent adverse events (TEAEs) are those that begin or worsen after the first dose through 30 days post-treatment, and include both serious and non-serious events.
Treatment-related TEAEs are those reasonably related to the study intervention.
Severity is graded per CTCAE v24.1:
Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe/medically significant), Grade 4 (life-threatening/disabling), Grade 5 (death related to AE).
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Approximately 2 years 11 months
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Part 1A and 1B: Number of Participants With Clinically Meaningful Change From Baseline in Laboratory Values
大体时间：Approximately 2 years 11 months
|
Number of participants with clinically meaningful change from baseline in laboratory parameters were reported.
Clinically meaningful abnormalities (identified as laboratory values having CTCAE grades >= 3).
Laboratory investigation included hematology, biochemistry, urinalysis, and coagulation.
|
Approximately 2 years 11 months
|
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Part 1A and 1B: Number of Participants With Clinically Meaningful Change From Baseline in Electrocardiogram (ECG)
大体时间：Approximately 2 years 11 months
|
Number of participants with clinically significant change from baseline in ECG parameters were reported.
Clinical Significance was decided by the investigator.
The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position.
The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.
|
Approximately 2 years 11 months
|
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Part 1A and 1B: Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs
大体时间：Approximately 2 years 11 months
|
Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate.
Clinical Relevance was decided by the investigator.
Number of participants with clinically relevant change from baseline in vital signs were reported.
Clinical relevance was defined as increase more than equal to (>=) 3° temperature, >40 beats heart rate increase, >40 mmHG increase in systolic or diastolic blood pressure, >10 breaths in respiratory rate increase.
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Approximately 2 years 11 months
|
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Part 1A and 1B: Number of Participants With Worsened Post Baseline Shift in Eastern Cooperative Oncology Group Performance Status
大体时间：Approximately 2 years 11 months
|
The number of participants who experienced worse post baseline shift were assessed as per ECOG performance status score recorded during the treatment.
The ECOG score is categorized as Grade 0, 1, 2, 3 and 4 where Grade 0=fully active, Grade 1=restricted in physically strenuous activity, Grade 2=unable to carry out any work activities, Grade 3=capable of only limited self-care and Grade 4=completely disabled.
|
Approximately 2 years 11 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M6223
大体时间：Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
Area under the serum concentration-time curve from time zero to the last sampling time at which the concentration is at or above lower limit of quantification (LLQ).
AUC0-t was calculated according to the mixed log linear trapezoidal rule.
The full form of unit of measure h*mcg/mL is hours · micrograms per milliliter.
|
Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
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Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of M6223
大体时间：Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
Area under the serum concentration time curve from time zero to infinity, calculated as AUC0 t + AUCextra.
AUCextra represents an extrapolated value obtained by Clast/λz, where Clast is the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above LLQ and λz is elimination rate constant.
|
Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
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Part 1A and Part 1B: Area Under Serum Concentration-Time Curve Over a Dosing Interval From Time Zero to Tau (AUC-tau) of M6223
大体时间：Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycle 1 (Cycle is of 21 days in Q3W regimen)
|
Area under the concentration-time curve from time zero up to time Tau, where Tau is the dosing interval.
|
Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycle 1 (Cycle is of 21 days in Q3W regimen)
|
|
Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223
大体时间：Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual participants.
|
Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
|
Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223
大体时间：Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
Ctrough is the concentration prior to study drug administration.
|
Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
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Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223
大体时间：Cycle 1 and 2: Day 1 (-2h, EOI, 4-6h), Day 2 (25-31h), Day 5 (±1h), Day 8 (±1h); Cycle 3 to end of treatment: Day 1 (-2h pre-dose only)
|
Time taken to reach maximum concentration of M66223 after admistration is reported.
|
Cycle 1 and 2: Day 1 (-2h, EOI, 4-6h), Day 2 (25-31h), Day 5 (±1h), Day 8 (±1h); Cycle 3 to end of treatment: Day 1 (-2h pre-dose only)
|
|
Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223
大体时间：Cycle 1 and 2: Day 1 (-2h, EOI, 4-6h), Day 2 (25-31h), Day 5 (±1h), Day 8 (±1h); Cycle 3 to end of treatment: Day 1 (-2h pre-dose only)
|
Terminal half-life is the time measured for the concentration to decrease by one half.
Terminal half-life is calculated by dividing the natural logarithm to the base e (Log e) multiplied by (*) 2/ λz, where 'λz' is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
|
Cycle 1 and 2: Day 1 (-2h, EOI, 4-6h), Day 2 (25-31h), Day 5 (±1h), Day 8 (±1h); Cycle 3 to end of treatment: Day 1 (-2h pre-dose only)
|
|
Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223
大体时间：Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
Elimination rate constant was obtained from linear regression of the terminal phase of the log transformed concentration-time data.
|
Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)
|
|
Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa
大体时间：Day 1 of Treatment of Cycles 1 and 4 from time zero to 14 days postdose
|
Maximum measured serum concentration, calculated from the serum concentration vs. time profile of the individual participants.
|
Day 1 of Treatment of Cycles 1 and 4 from time zero to 14 days postdose
|
|
Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp Alfa
大体时间：Day 1 of Treatment of Cycles 1 and 4 from time zero to 14 days postdose
|
Ctrough is the concentration prior to study drug administration.
|
Day 1 of Treatment of Cycles 1 and 4 from time zero to 14 days postdose
|
|
Part IA and 1B: Number of Participants With Positive Antidrug Antibody (ADA) Assays
大体时间：Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit ( approximately 2 years 11 months)
|
Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA).
Number of participants with positive ADA were reported.
|
Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit ( approximately 2 years 11 months)
|
|
Part 1A and IB: Best Overall Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator
大体时间：From first study drug administration until documented disease progression or death due to any cause whichever occurs first (approximately 2 years 11 months)
|
The ORR is defined as the number of participants with a documented BOR (complete response (CR) or partial response (PR)) by the investigator during treatment with avelumab plus axitinib as firstline therapy.
The BOR is defined as the best tumor response recorded during the observation period.
The definitions of tumor responses are as follows: Complete or PR as the best adjudication result (CR > PR > stable disease [SD] > progressive disease [PD], not Evaluable [NE]) complies with the RECIST tumor assessment guidelines as closely as possible in clinical practice.
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first (approximately 2 years 11 months)
|
|
Part 1A and 1B: Duration of Response (DOR) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator
大体时间：From first study drug administration until documented disease progression or death due to any cause whichever occurs first( approximately 2 years 11 months)
|
DOR was defined for participants with a confirmed objective response as the time from first documentation of a confirmed objective response (CR or PR) according to RECIST 1.1 to the date of first documentation of objective PD or death due to any cause, whichever occurs first.
CR: Disappearance of all evidence of target and non-target lesions.
PR: At least 30 percent (%) reduction from baseline in sum of longest diameter (SLD) of all lesions.
PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.
DOR was determined according to RECIST v1.1 and assessed by IRC.
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first( approximately 2 years 11 months)
|
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Part 1A and 1B: Time to Tumor Response (TTR) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator
大体时间：From first study drug administration until documented disease progression or death due to any cause whichever occurs first (approximately 2 years 11 months))
|
TTR was defined for participants who achieved objective response as time from first study drug administration to first documentation of objective tumor response (CR or PR) that was subsequently confirmed.
CR was defined as a score of 1 (no uptake above background), 2 (uptake <= mediastinum), or 3 (uptake <mediastinum but <=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites; no new lesions; no evidence of FDG-avid disease in bone marrow.
PR was defined as >=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >=50% decrease in SPD of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease.
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first (approximately 2 years 11 months))
|
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Part 1A and 1B: Disease Control According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator
大体时间：From first study drug administration until documented disease progression or death due to any cause whichever occurs first (approximately 2 years 11 months))
|
Disease control rate was defined as percentage of participants with disease control.
Disease Control (DC) was defined as the best overall response of CR, PR, or stable disease (SD).
CR: score of 1 (no uptake above background), 2 (uptake <= mediastinum), or 3 (uptake less than <mediastinum but <=liver) with or without a residual mass on Positron Emission Tomography 5-Point Scale, for lymph nodes and extra lymphatic sites; no new lesions; no evidence of fluorodeoxyglucose -avid disease in bone marrow.
PR: >=50% decrease in SPD of up to six of the largest dominant lymph nodes, no increase in size of other nodes, liver, or spleen volume, a >=50% decrease in Sum of the Products of Diameters of hepatic and splenic nodules, absence of other organ involvement, and no new sites of disease.
SD: <50% decrease in SDP of up to 6 dominant, measurable nodes and extranodal sites; no criteria for progressive disease met.
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first (approximately 2 years 11 months))
|
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Part 1A and 1B: Progression-free Survival Time According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator
大体时间：From first study drug administration until documented disease progression or death due to any cause whichever occurs first (approximately 2 years 11 months)
|
Progression Free Survival (PFS) time is defined as the time from start date of treatment to the date of the first documentation of objective progression of disease (PD) or death due to any cause, whichever occurs first.
The tumor response will be determined according to RECIST 1.1 and assessed by the investigator.
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first (approximately 2 years 11 months)
|
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Part 1A and 1B: Overall Survival
大体时间：From first study drug administration to the date of death due to any cause (approximately 2 years 11 months)
|
Overall survival was defined as the time (in months) from first study drug administration to the date of death due to any cause.
Participants last known to be alive were censored at date of last contact.
Analysis was performed using Kaplan-Meier method.
|
From first study drug administration to the date of death due to any cause (approximately 2 years 11 months)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 研究主任：Medical Responsible、Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
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研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2020年7月10日
初级完成 (实际的)
2023年6月23日
研究完成 (实际的)
2023年6月23日
研究注册日期
首次提交
2020年6月30日
首先提交符合 QC 标准的
2020年6月30日
首次发布 (实际的)
2020年7月7日
研究记录更新
最后更新发布 (实际的)
2026年5月4日
上次提交的符合 QC 标准的更新
2026年4月13日
最后验证
2026年4月1日
更多信息
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