A Phase Ia/Ib Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of HDM2005 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Recommended Phase 2 Dose (RP2D) (for dose expansion phase) Recommended Phase 2 Dose (RP2D) (for dose expansion phase) Recommended Phase 2 Dose (RP2D) (for dose expansion phase)
研究概览
简要总结
This is a study evaluating the efficacy, safety, and pharmacokinetics ofHDM2005 in participants with metastatic solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Agree to follow the study treatment protocol and visit schedule, enroll voluntarily and sign a written informed consent.
- •Male or female aged ≥ 18 years at the time of signing the ICF;
- •ECOG performance status of 0-
- •Life expectancy of at least 3 months.
- •Specific types of advanced solid tumors that have been confirmed by histopathological examination.
- •Has metastatic disease that has progressed during or following previous treatment appropriate for the disease type.
- •All subjects are required to provide archived tissue (5 unstained sections) obtained within the previous 2 years or fresh tissue for ROR1 expression testing at the central laboratory.
- •Presence of radiographically measurable disease.
- •Subjects must have recovered (to ≤ Grade 1) from any AE associated with prior anticancer therapy.
- •Has adequate organ function.
- •Female subjects of childbearing potential should agree to use contraception methods during the study and for 6 months after the end of the study; have a negative serum pregnancy test within 7 days before study enrollment; and male subjects should agree to use contraceptive avoidance measures during the study and for 6 months after the end of the study.
排除标准
- •Patients with active brain metastases (defined as stable for < 4 weeks, or symptomatic, or requiring antiepileptic drug/hormonal therapy, or meningeal metastases).
- •Subjects have another primary malignancy ,with the following exceptions: adequately treated non-melanoma skin cancer without evidence of disease recurrence and adequately treated carcinoma in situ without evidence of disease recurrence,et al.
- •History of severe bleeding disorders .
- •History of chronic pancreatitis or acute pancreatitis within 6 months.
- •History of interstitial lung disease, radiation pneumonitis requiring steroid therapy, or any evidence of clinically active interstitial lung disease.
- •Patients with uncontrolled pleural effusion, pericardial effusion or ascites requiring repeated drainage after intubation and drainage,VEGF inhibitors, platinum and other drugs injection (subjects with stable symptoms for at least one week after treatment can be enrolled).
- •Prior solid organ transplantation.
- •Has peripheral neuropathy of Grade >
- •Has significant cardiovascular or cerebrovascular diseases.
- •Has an uncontrolled ongoing infection.
- •Active infectious disease, such as HIV infection, active hepatitis B, active hepatitis C (positive RNA result), active syphilis.
- •Receiving corticosteroids (prednisone equivalent more than10 mg/day).
- •Contraindication to any component of HDM
- •History of drug anaphylactic shock, severe food allergy, uncontrolled asthma or COPD.
- •Female subjects who are pregnant, lactating or planning to become pregnant during the study.
- •Known history of mental illness or substance abuse that would impair the subject's ability to cooperate with study requirements.
- •Prior or current evidence of any disease, treatment, or laboratory abnormality that, in the opinion of the investigator, could affect the outcome of the study, prevent the subject from participating in the study entirely, or is not in the subjects' best interest.
研究组 & 干预措施
HDM2005
In dose escalation phase, participants will be administered escalating doses of HDM2005 at 1.8~2.5mg/kg IV on Day 1 of repeated 21-day cycles or 1.2~2.0mg/kg IV on Day 1 of repeated 14-day cycles .
In dose expansion phase, participants will be administered to recommended dose for expansion (RDE) of HDM2005 .
干预措施: HDM2005 (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D) (for dose expansion phase) Recommended Phase 2 Dose (RP2D) (for dose expansion phase) Recommended Phase 2 Dose (RP2D) (for dose expansion phase)
时间窗: Approximately 30 months
The selection of RP2D will be based on consideration of overall safety information together with available pharmacokinetic,E-R relationships, and efficacy data. The selection of RP2D will be based on consideration of overall safety information together with available pharmacokinetic and efficacy data.
Incidence of dose limiting toxicity (DLT) events (for dose escalation phase)
时间窗: up to 21 days or 28 days following first dose
DLT will be determined by definition during the DLT observation period.
Incident and severity of adverse events(for dose escalation phase)
时间窗: Until 28 days after the last dose or initiation of a new antineoplastic therapy, whichever occurs first.
The safety profile of HDM2005 will be assessed by monitoring the adverse events (AE) per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0.
Progression-free survival(PFS)(for dose expansion phase)
时间窗: Approximately 30 months
PFS, defined as the interval from the start of study treatment to the earlier of the first documentation of disease progression or death from any cause per RECIST, Version 1.1.
Objective Response Rate (ORR)(for dose expansion phase)
时间窗: Approximately 18 months
Objective response rate (ORR), which includes best response of complete response (CR) or partial response (PR) as assessed by the investigator.
次要结局
- Immunogenicity(up to 28 days following last dose)
- Objective Response Rate (ORR)(for dose escalation phase)(Approximately 18 months)
- Time to Response (TTR)(Approximately 30 months)
- Duration of Response (DOR)(Approximately 30 months)
- Overall survival (OS)(Approximately 30 months)
- Plasma concentration of HDM2005, total antibody and the free MMAE(up to 28 days following last dose)