A Multi-center, Non-randomized, and Open-label Phase I/IIa Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of ICP-490 in Patients With Relapsed and/or Refractory Multiple Myeloma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 80
- 试验地点
- 6
- 主要终点
- Phase I : Incidence, type, and severity of adverse events (AEs) as judged according to NCI-CTCAE V5.0
研究概览
简要总结
This is a multi-center, non-randomized and open-label phase I/IIa clinical study to evaluate the safety, tolerability, and efficacy of ICP-490 in patients with relapsed and/or refractory multiple myeloma.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years old.
- •Diagnosed as relapsed and/or refractory multiple myeloma .The patient must have measurable diseases.Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0-
- •Patients must have adequate organ function. Expected survival time ≥ 6 months.
- •All toxicities caused by prior anticancer therapy must have recovered to Grade ≤ 1 (based on CTCAE v5.0) except alopecia and fatigue.
- •Female patients of childbearing potential should have a negative blood pregnancy test result within 48 h prior to the first dose of investigational drug.
排除标准
- •Known active central nervous system (CNS) involvement or history of the disease, or clinical signs of multiple myeloma meningeal/spinal meningeal involvement.
- •Patients with solitary plasmacytoma; plasma cell leukemia (PCL) (active PCL or history of PCL); Waldenström's macroglobulinemia; POEMS syndrome or symptomatic amyloidosis.
- •Prior active or history of malignancies other than MM, occurring within 5 years prior to the first dose of investigational drug, with the exception of radically treated local curable cancers.
- •Uncontrolled or severe cardiovascular disorders.
- •Any active infection within 14 days prior to the first dose of investigational drug.
- •Patients with diseases restricted from participation as described in the protocol
- •Having undergone major surgery within 28 days prior to the first dose of investigational drug, or minor surgery within 2 weeks prior to the first dose. Any severe or uncontrolled systemic disease evaluated by investigatorthat may increase the risk associated with study participation and drug administration or affect the patient's ability to receive the investigational drug.
- •Patients who have received any other systemic treatment, anti-tumor traditional Chinese (herbal) medicine therapy , and any other investigational drug therapy for MM within 28 days or 5 half-lives of the drugs (whichever is shorter) prior to the first dose of investigational drug.
- •Patients who have received systemic treatment with corticosteroids or other immunosuppressive drugs within 14 days prior to the first dose of investigational drug.
- •Subjects are allowed to use topical, ocular, intra-articular, intranasal, and inhaledcorticosteroid ; short-term use (≤ 7 days) of corticosteroid for prophylaxis (e.g., contrast agent allergy) or for the treatment of non-autoimmune diseases (e.g., delayed hypersensitivity reaction caused by contact allergens) is permitted.
- •Patients who have received medications or foods with strong inhibitory or inductive effects on cytochrome P450 CYP3A, and proton pump inhibitorswithin 2 weeks prior to the first dose of investigational drug, or are planning to receive them during the study.
- •Patients with a history of severe allergic reactions to IMIDs , or dexamethasone, or to any component contained in ICP-490 or dexamethasone formulation (CTCAE V5.0 Grade > 3).
研究组 & 干预措施
ICP-490
干预措施: ICP-490 (Drug)
ICP-490 in combination with Dexamethasone
干预措施: ICP-490 (Drug)
ICP-490 in combination with Dexamethasone
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Phase I : Incidence, type, and severity of adverse events (AEs) as judged according to NCI-CTCAE V5.0
时间窗: Through study completion, an average of 3 years
AE refers to any adverse event occurring in subjects during clinical research period. The incidence and type of AEs will be evaluated and the severity will be judged according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version5.0.
Phase I : Incidence, type, and severity of dose-limiting toxicities (DLTs)
时间窗: Through study completion, an average of 3 years
The dose-limiting toxicity (DLT) assessed in the phase I dose exploration study is defined as AEs related to study treatment that meet the following criteria (according to the NCI CTCAE v5.0 criteria) and occur in Cycle 1.
Phase I : RP2Ds and/or MTDs
时间窗: Through study completion, an average of 3 years
Phase I is the dose exploration study of ICP-490 to preliminarily determine RP2Ds (probably more than one) and MTD (if applicable). MTD: The dose level corresponding to the dose group whose posterior probability of DLT incidence estimated by PAVA (pool adjacent violators algorithm) is closest to the target toxicity probability (25%).
Phase II : ORR (defined as sCR + CR + VGPR + PR) assessed according to IMWG criteria.
时间窗: Through study completion, an average of 3 years
Disease response will be assessed according to the 2016 IMWG response criteria.
次要结局
- Time to maximum concentration (Tmax)(Through study completion, an average of 3 years)
- Half-life (T1/2)(Through study completion, an average of 3 years)
- Area under the concentration-time curve (AUC0-∞ and AUC0-t)(Through study completion, an average of 3 years)
- Apparent clearance (CL/F)(Through study completion, an average of 3 years)
- Apparent volume of distribution during terminal phase (Vz/F)(Through study completion, an average of 3 years)
- Maximum concentration (Cmax)(Through study completion, an average of 3 years)
- Steady-state PK parameters(Through study completion, an average of 3 years)
- The overall response rate (ORR) assessed according to the International Myeloma Working Group (IMWG) criteria (ORR, defined as stringent complete response (sCR) + complete response (CR) + very good partial response (VGPR) + partial response (PR))(Through study completion, an average of 3 years)
- Phase I & IIa : Complete response rate (CRR, defined as sCR + CR) assessed according to IMWG criteria(Through study completion, an average of 3 years)
- Phase I & IIa : Very good or better partial response rate assessed according to IMWG criteria (≥ VGPR rate, defined as VGPR + sCR + CR)(Through study completion, an average of 3 years)
- Phase I & IIa : Time to response (TTR) assessed according to IMWG criteria(Through study completion, an average of 3 years)
- Phase I & IIa : Duration of response (DOR) assessed according to IMWG criteria(Through study completion, an average of 3 years)
- Phase I & IIa : Progression-free survival (PFS) assessed according to IMWG criteria(Through study completion, an average of 3 years)
- Phase I & IIa : Overall survival (OS)(Through study completion, an average of 3 years)