A Phase I/II Clinical Study to Evaluate the Efficacy and Safety of MHB036C for Injection Combined With Other Anti-tumor Therapy in Patients With Advanced Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- (Dose-Escalation Stage): Maximum tolerated dose (MTD) for MHB036C and other anti-tumor treatment combination therapy
研究概览
简要总结
This is a first-in-human, open-label, multicenter Phase I/II study of MHB036C combined with MHB039A or other anti-tumor therapy in patients with advanced lung cancer. The study was designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of MHB036C combined with MHB039A or other anti-tumor therapies.
详细描述
This first-in-human clinical trial of MHB036C combined with MHB039A or other anti-tumor therapy comprises two parts: a dose escalation phase and dose 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 MHB036C combining different anti-tumor treatment regimens (including Furmonertinib, MHB039A for injection, and Carboplatin) in patients with advanced lung cancer, 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 dose expansion phase to further evaluate the safety and efficacy of MHB036C combined with MHB039A or other anti-tumor therapy in patients with specific types of advanced lung cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntarily agrees to participate in the study and signs the informed consent form.
- •Age ≥ 18 years and≤75 years, no restriction on gender.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •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.
排除标准
- •Small cell lung cancer (SCLC) components in the histopathology.
- •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 first study dose.
- •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 impairment of pulmonary function; interstitial lung disease or a history of pneumonia requiring steroid treatment; previous left or right pneumonectomy.
- •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. -
研究组 & 干预措施
Dose escalation: cohort 1
Subjects will receive MHB036C Q3W by intravenous administration in combination with Furmonertinib QD by oral administration.
干预措施: MHB036C for Injection (Drug)
Dose escalation: cohort 1
Subjects will receive MHB036C Q3W by intravenous administration in combination with Furmonertinib QD by oral administration.
干预措施: Furmonertinib (Drug)
Dose escalation: cohort 2
Subjects will receive MHB036C Q3W in combination with MHB039A Q3W by intravenous administration
干预措施: MHB036C for Injection (Drug)
Dose escalation: cohort 2
Subjects will receive MHB036C Q3W in combination with MHB039A Q3W by intravenous administration
干预措施: MHB039A for Injection (Drug)
Dose escalation: cohort 3
Subjects will receive MHB036C Q3W in combination with Carboplatin AUC 5mg/mL/min by intravenous administration
干预措施: MHB036C for Injection (Drug)
Dose escalation: cohort 3
Subjects will receive MHB036C Q3W in combination with Carboplatin AUC 5mg/mL/min by intravenous administration
干预措施: Carboplatin (Drug)
Dose expansion: cohort 4
Subjects will receive MHB036C Q3W by intravenous administration in combination with Furmonertinib QD by oral administration.
干预措施: MHB036C for Injection (Drug)
Dose expansion: cohort 4
Subjects will receive MHB036C Q3W by intravenous administration in combination with Furmonertinib QD by oral administration.
干预措施: Furmonertinib (Drug)
Dose expansion: cohort 5
Subjects will receive MHB036C Q3W in combination with MHB039A Q3W by intravenous administration
干预措施: MHB036C for Injection (Drug)
Dose expansion: cohort 5
Subjects will receive MHB036C Q3W in combination with MHB039A Q3W by intravenous administration
干预措施: MHB039A for Injection (Drug)
Dose expansion: cohort 6
Subjects will receive MHB036C Q3W in combination with Carboplatin AUC 5mg/mL/min by intravenous administration
干预措施: MHB036C for Injection (Drug)
Dose expansion: cohort 6
Subjects will receive MHB036C Q3W in combination with Carboplatin AUC 5mg/mL/min by intravenous administration
干预措施: Carboplatin (Drug)
结局指标
主要结局
(Dose-Escalation Stage): Maximum tolerated dose (MTD) for MHB036C and other anti-tumor treatment combination therapy
时间窗: Up to day 21 from the first dose for Q3W administration.
To determine the MTD for further evaluation of MHB036C and other anti-tumor treatment combination therapy
(Dose-Escalation Stage): Incidence and severity of adverse events (AEs)
时间窗: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years.
AE assessed by investigator exclusively related to subject's underlying disease or medical condition \[graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0\].
(Dose-Expansion Stage): Objective tumor response (ORR) determined by investigators according to RECIST v1.1
时间窗: Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years
Objective tumor response for target lesions will be assessed by imaging/measurement compared with the overall tumor burden at baseline (Day -28 to -1). ORR is evaluated by the number of participants with best overall response of CR and PR (Confirmed CR/PR assessment require at least 1 repeat).
次要结局
- Pharmacokinetic (PK) parameters of total antibody, ADC, and free toxin at various time points(From pre-dose to 22 days after the first dose)
- Duration of response (DOR) determined by investigators according to RECIST v1.1(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(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(Baseline up until documented progressive disease, death, lost to follow-up, or withdrawal by the participant, up to approximately 5 years)