A Phase Ia/Ib, Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of HDM2005 in Patients With Relapsed/Refractory B-cell Lymphoma and Advanced Solid Tumor
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 111
- 试验地点
- 8
- 主要终点
- Incidence of dose limiting toxicity (DLT) events (for dose escalation phase)
研究概览
简要总结
This is a first-in-human (FIH) study to evaluate the safety and preliminary efficacy of experimental drug HDM2005 in patients with relapsed/refractory B-cell lymphoma and advanced 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;
- •B-cell lymphoma: ECOG performance status of 0-2;
- •Advanced solid tumors: ECOG performance status of 0-1;
- •Life expectancy of at least 3 months;
- •Dose escalation phase: Histopathologically confirmed relapsed/refractory B-cell lymphoma following at least 2 prior lines of systemic therapy;
- •Dose expansion phase: relapsed/refractory B-cell lymphoma and advanced or metastatic solid tumor of specified 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; in addition, relapsed/refractory lymphoma subjects are required to provide tissue sections used for previous pathological diagnosis for pathological consultation at the central laboratory;
- •Relapsed/refractory B-cell lymphoma: Subjects in Phase Ia dose escalation phase should have evaluable lesions; subjects in Phase Ib dose expansion phase should have at least 1 radiographically measurable lymph node or extranodal malignant tumor lesion (intranodal lesion defined as having a long diameter > 1.5 cm; extranodal lesion having a long diameter > 1.0 cm) as assessed by computed tomography (CT)/magnetic resonance imaging (MRI) according to 2014 Lugano criteria, and a lesion that has previously received radiotherapy is considered measurable when it shows unequivocal progression after completion of radiotherapy;
- •Advanced solid tumors: subjects are required to have at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 ;
- •Subjects must have recovered (to ≤ Grade 1) from any AE associated with prior anticancer therapy;
- •Subjects have adequate organ and bone marrow function;
- •Female subjects of childbearing potential should agree to use contraception methods (e.g., intrauterine device, contraceptive pill, or condom) 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
- •B-cell lymphoma: known central nervous system (CNS) involvement .
- •Advanced solid tumors: Patients with active brain metastases (defined as stable for < 4 weeks, or symptomatic, or requiring antiepileptic drug/hormonal therapy, or meningeal metastases);
- •Subjects with prior allogeneic HSCT who have developed acute graft-versus-host disease (GVHD) or persistent evidence of chronic GVHD (as manifested by ≥ Grade 2 serum bilirubin, ≥ Grade 3 skin involvement, or ≥ Grade 3 diarrhea or receiving systemic immunosuppressive therapy/prophylaxis for GVHD);
- •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;
- •Persistent peripheral neuropathy > Grade 1 at baseline;
- •Clinically significant cardiovascular or cerebrovascular diseases;
- •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic therapy (except for localized skin or nail bed fungal infection) at enrollment;
- •Active infectious disease, such as HIV infection, active hepatitis B, active hepatitis C (positive RNA result), active syphilis;
- •Receiving corticosteroids (prednisone equivalent more than 30 mg/day);
- •Contraindication to any component of HDM2005;
- •History of drug anaphylactic shock, severe food allergy, uncontrolled asthma/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 0.3~2.75mg/kg IV on Day 1 of repeated 21-day cycles.
In dose expansion phase, participants will be administered to recommended dose for expansion (RDE) of HDM2005 on Day 1 of repeated 21-day cycles .
干预措施: HDM2005 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicity (DLT) events (for dose escalation phase)
时间窗: up to 21 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.
Objective Response Rate (ORR)(for dose expansion phase)
时间窗: Until withdrawal of consent, loss to follow-up, initiation of other new antineoplastic therapy, end of study, or study termination by the sponsor, whichever occurs first (up to approximately 3.5 years)
Objective response rate (ORR), which includes best response of complete response (CR) or partial response (PR) as assessed by the investigator.
Recommended Phase 2 Dose (RP2D) (for dose expansion phase)
时间窗: Approximately 3.5 years
The selection of RP2D will be based on consideration of overall safety information together with available pharmacokinetic,E-R relationships, and efficacy data.
次要结局
- Plasma concentration of HDM2005, total antibody and the free MMAE(up to 28 days following last dose)
- Immunogenicity(up to 28 days following last dose)
- Incident and severity of adverse events(for dose expansion phase)(Until 28 days after the last dose or initiation of a new antineoplastic therapy, whichever occurs first)
- Objective Response Rate (ORR)(for dose escalation phase)(Approximately 3.5 years)
- Time to Response (TTR)(Approximately 3.5 years)
- Progression free survival (PFS)(Approximately 3.5 years)
- Duration of Response (DOR)(Approximately 3.5 years)
- Overall survival (OS)(Approximately 3.5 years)