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Evaluate the Safety, Tolerability, and Efficacy of ICP-490 in Patients With Relapsed and/or Refractory Multiple Myeloma

Primary Purpose

Relapsed and/or Refractory Multiple Myeloma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
ICP-490
Sponsored by
Beijing InnoCare Pharma Tech Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed and/or Refractory Multiple Myeloma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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. Presence or history of clinically significant CNS diseases or pathological changes.Any active infection within 14 days prior to the first dose of investigational drug. Patients with active HBV,HCV,HIV infection. Subjects with clinically significant gastrointestinal anomalies that may affect drug intake, transport, or absorption. 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 (dose equivalent to > 10 mg/day prednisone) 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).

Sites / Locations

  • Peking University People's HospitalRecruiting
  • Henan Cancer Hosptital
  • Shengjing Hospital of China Medical University
  • Renji Hospital, Shanghai Jiao Tong University School of Medicine
  • The First Affiliated Hospital,Zhejiang University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ICP-490

Arm Description

ICP-490 is administered continuously on Days 1-21, QD in every 28-day cycle. Patients who develop progressive disease (PD) at any timepoint during ICP-490 treatment, or who do not respond after completing 4 treatment cycles, dexamethasone can be added to the current ICP-490 dose level.

Outcomes

Primary Outcome Measures

Phase I : Incidence, type, and severity of adverse events (AEs) as judged according to NCI-CTCAE V5.0
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)
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
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.
Disease response will be assessed according to the 2016 IMWG response criteria.

Secondary Outcome Measures

Maximum concentration (Cmax)
Maximum concentration (Cmax) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Time to maximum concentration (Tmax)
Time to maximum concentration (Tmax) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Half-life (T1/2)
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)
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)
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)
Apparent volume of distribution during terminal phase (Vz/F) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Steady-state PK parameters
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))
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
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)
Disease response will be assessed according to the 2016 IMWG response criteria.
Phase I & IIa : Time to response (TTR) assessed according to IMWG criteria
Disease response will be assessed according to the 2016 IMWG response criteria
Phase I & IIa : Duration of response (DOR) assessed according to IMWG criteria
Disease response will be assessed according to the 2016 IMWG response criteria
Phase I & IIa : Progression-free survival (PFS) assessed according to IMWG criteria
Disease response will be assessed according to the 2016 IMWG response criteria
Phase I & IIa : Overall survival (OS)
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.

Full Information

First Posted
January 10, 2023
Last Updated
April 14, 2023
Sponsor
Beijing InnoCare Pharma Tech Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05719701
Brief Title
Evaluate the Safety, Tolerability, and Efficacy of ICP-490 in Patients With Relapsed and/or Refractory Multiple Myeloma
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 29, 2023 (Actual)
Primary Completion Date
July 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Beijing InnoCare Pharma Tech Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed and/or Refractory Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ICP-490
Arm Type
Experimental
Arm Description
ICP-490 is administered continuously on Days 1-21, QD in every 28-day cycle. Patients who develop progressive disease (PD) at any timepoint during ICP-490 treatment, or who do not respond after completing 4 treatment cycles, dexamethasone can be added to the current ICP-490 dose level.
Intervention Type
Drug
Intervention Name(s)
ICP-490
Intervention Description
The initial dose of ICP-490 is 0.1 mg, five dose groups are planned for the dose exploration (0.1 mg to 1.5 mg).
Primary Outcome Measure Information:
Title
Phase I : Incidence, type, and severity of adverse events (AEs) as judged according to NCI-CTCAE V5.0
Description
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.
Time Frame
Through study completion, an average of 3 years
Title
Phase I : Incidence, type, and severity of dose-limiting toxicities (DLTs)
Description
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.
Time Frame
Through study completion, an average of 3 years
Title
Phase I : RP2Ds and/or MTDs
Description
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%).
Time Frame
Through study completion, an average of 3 years
Title
Phase II : ORR (defined as sCR + CR + VGPR + PR) assessed according to IMWG criteria.
Description
Disease response will be assessed according to the 2016 IMWG response criteria.
Time Frame
Through study completion, an average of 3 years
Secondary Outcome Measure Information:
Title
Maximum concentration (Cmax)
Description
Maximum concentration (Cmax) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Time Frame
Through study completion, an average of 3 years
Title
Time to maximum concentration (Tmax)
Description
Time to maximum concentration (Tmax) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Time Frame
Through study completion, an average of 3 years
Title
Half-life (T1/2)
Description
Half-life (T1/2) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Time Frame
Through study completion, an average of 3 years
Title
Area under the concentration-time curve (AUC0-∞ and AUC0-t)
Description
Area under the concentration-time curve (AUC0-∞ and AUC0-t) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Time Frame
Through study completion, an average of 3 years
Title
Apparent clearance (CL/F)
Description
Apparent clearance (CL/F) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Time Frame
Through study completion, an average of 3 years
Title
Apparent volume of distribution during terminal phase (Vz/F)
Description
Apparent volume of distribution during terminal phase (Vz/F) will be calculated through multiple plasma concentrations drawn from the patients after administration.
Time Frame
Through study completion, an average of 3 years
Title
Steady-state PK parameters
Description
Steady-state PK parameters will be calculated through multiple plasma concentrations drawn from the patients after administration.
Time Frame
Through study completion, an average of 3 years
Title
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))
Description
Disease response will be assessed according to the 2016 IMWG response criteria.
Time Frame
Through study completion, an average of 3 years
Title
Phase I & IIa : Complete response rate (CRR, defined as sCR + CR) assessed according to IMWG criteria
Description
Disease response will be assessed according to the 2016 IMWG response criteria.
Time Frame
Through study completion, an average of 3 years
Title
Phase I & IIa : Very good or better partial response rate assessed according to IMWG criteria (≥ VGPR rate, defined as VGPR + sCR + CR)
Description
Disease response will be assessed according to the 2016 IMWG response criteria.
Time Frame
Through study completion, an average of 3 years
Title
Phase I & IIa : Time to response (TTR) assessed according to IMWG criteria
Description
Disease response will be assessed according to the 2016 IMWG response criteria
Time Frame
Through study completion, an average of 3 years
Title
Phase I & IIa : Duration of response (DOR) assessed according to IMWG criteria
Description
Disease response will be assessed according to the 2016 IMWG response criteria
Time Frame
Through study completion, an average of 3 years
Title
Phase I & IIa : Progression-free survival (PFS) assessed according to IMWG criteria
Description
Disease response will be assessed according to the 2016 IMWG response criteria
Time Frame
Through study completion, an average of 3 years
Title
Phase I & IIa : Overall survival (OS)
Description
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.
Time Frame
Through study completion, an average of 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. Exclusion Criteria: 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. Presence or history of clinically significant CNS diseases or pathological changes.Any active infection within 14 days prior to the first dose of investigational drug. Patients with active HBV,HCV,HIV infection. Subjects with clinically significant gastrointestinal anomalies that may affect drug intake, transport, or absorption. 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 (dose equivalent to > 10 mg/day prednisone) 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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
April Huang
Phone
010-66609723
Email
April.huang@innocarepharma.com
Facility Information:
Facility Name
Peking University People's Hospital
City
Beijing
State/Province
Beijing
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiaojun Huang, PhD
Facility Name
Henan Cancer Hosptital
City
Zhengzhou
State/Province
Henan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Baijun Fang
Facility Name
Shengjing Hospital of China Medical University
City
Shenyang
State/Province
Liaoning
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aijun Liao, PhD
Facility Name
Renji Hospital, Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lijing Shen
Facility Name
The First Affiliated Hospital,Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhen Cai, PhD

12. IPD Sharing Statement

Learn more about this trial

Evaluate the Safety, Tolerability, and Efficacy of ICP-490 in Patients With Relapsed and/or Refractory Multiple Myeloma

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