Evaluate the Safety, Tolerability, and Efficacy of ICP-490 in Patients With Relapsed and/or Refractory Multiple Myeloma
- Conditions
- Relapsed and/or Refractory Multiple Myeloma
- Interventions
- Registration Number
- NCT05719701
- Lead Sponsor
- Beijing InnoCare Pharma Tech Co., Ltd.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
- 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 0-2.
- 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.
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Known active central nervous system (CNS) involvement or history of the disease, or clinical signs of multiple myeloma meningeal/spinal meningeal involvement.
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Patients with solitary plasmacytoma; plasma cell leukemia (PCL) (active PCL or history of PCL); Waldenström's macroglobulinemia; POEMS syndrome or symptomatic amyloidosis.
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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.
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Uncontrolled or severe cardiovascular disorders.
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Any active infection within 14 days prior to the first dose of investigational drug.
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Patients with diseases restricted from participation as described in the protocol
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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.
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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.
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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.
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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.
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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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description ICP-490 ICP-490 - ICP-490 in combination with Dexamethasone ICP-490 - ICP-490 in combination with Dexamethasone Dexamethasone -
- Primary Outcome Measures
Name Time Method Phase I : Incidence, type, and severity of adverse events (AEs) as judged according to NCI-CTCAE V5.0 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) 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 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. Through study completion, an average of 3 years Disease response will be assessed according to the 2016 IMWG response criteria.
- Secondary Outcome Measures
Name Time Method Time to maximum concentration (Tmax) Through study completion, an average of 3 years Time to maximum concentration (Tmax) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Half-life (T1/2) Through study completion, an average of 3 years Half-life (T1/2) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Area under the concentration-time curve (AUC0-∞ and AUC0-t) Through study completion, an average of 3 years Area under the concentration-time curve (AUC0-∞ and AUC0-t) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Apparent clearance (CL/F) Through study completion, an average of 3 years Apparent clearance (CL/F) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Apparent volume of distribution during terminal phase (Vz/F) Through study completion, an average of 3 years Apparent volume of distribution during terminal phase (Vz/F) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Phase I & IIa : Overall survival (OS) Through study completion, an average of 3 years The follow-up visits should be carried out every 12 weeks after the last dose via telephone or other methods to obtain the survival status information of patients.
Maximum concentration (Cmax) Through study completion, an average of 3 years Maximum concentration (Cmax) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Phase I & IIa : Time to response (TTR) assessed according to IMWG criteria Through study completion, an average of 3 years Disease response will be assessed according to the 2016 IMWG response criteria
Phase I & IIa : Duration of response (DOR) assessed according to IMWG criteria Through study completion, an average of 3 years Disease response will be assessed according to the 2016 IMWG response criteria
Phase I & IIa : Progression-free survival (PFS) assessed according to IMWG criteria Through study completion, an average of 3 years Disease response will be assessed according to the 2016 IMWG response criteria
Steady-state PK parameters Through study completion, an average of 3 years Steady-state PK parameters will be calculated through multiple plasma concentrations drawn from the patients after administration.
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 Disease response will be assessed according to the 2016 IMWG response criteria.
Phase I & IIa : Complete response rate (CRR, defined as sCR + CR) assessed according to IMWG criteria Through study completion, an average of 3 years Disease response will be assessed according to the 2016 IMWG response criteria.
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 Disease response will be assessed according to the 2016 IMWG response criteria.
Trial Locations
- Locations (6)
Sun Yat-sen University Cancer Center
🇨🇳Guangzhou, Guangdong, China
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
Renji Hospital, Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, Shanghai, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Henan Cancer Hosptital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital，Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China