Clinical trial NCT05719701: 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
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed and/or Refractory Multiple Myeloma
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-02-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Aged ≥ 18 years old.
2. 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.
3. Patients must have adequate organ function. Expected survival time ≥ 6 months.
4. 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:

1. Known active central nervous system (CNS) involvement or history of the disease, or clinical signs of multiple myeloma meningeal/spinal meningeal involvement.
2. Patients with solitary plasmacytoma; plasma cell leukemia (PCL) (active PCL or history of PCL); Waldenström's macroglobulinemia; POEMS syndrome or symptomatic amyloidosis.
3. 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.
4. Uncontrolled or severe cardiovascular disorders.
5. Any active infection within 14 days prior to the first dose of investigational drug.
6. Patients with diseases restricted from participation as described in the protocol
7. 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.
8. 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.
9. 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.
10. 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.
11. 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).

Primary outcomes:
measure: Phase I : Incidence, type, and severity of adverse events (AEs) as judged according to NCI-CTCAE V5.0
timeFrame: Through study completion, an average of 3 years
measure: Phase I : Incidence, type, and severity of dose-limiting toxicities (DLTs)
timeFrame: Through study completion, an average of 3 years
measure: Phase I : RP2Ds and/or MTDs
timeFrame: Through study completion, an average of 3 years
measure: Phase II : ORR (defined as sCR + CR + VGPR + PR) assessed according to IMWG criteria.
timeFrame: Through study completion, an average of 3 years
Secondary outcomes:
measure: Maximum concentration (Cmax)
timeFrame: Through study completion, an average of 3 years
measure: Time to maximum concentration (Tmax)
timeFrame: Through study completion, an average of 3 years
measure: Half-life (T1/2)
timeFrame: Through study completion, an average of 3 years
measure: Area under the concentration-time curve (AUC0-∞ and AUC0-t)
timeFrame: Through study completion, an average of 3 years
measure: Apparent clearance (CL/F)
timeFrame: Through study completion, an average of 3 years
measure: Apparent volume of distribution during terminal phase (Vz/F)
timeFrame: Through study completion, an average of 3 years
measure: Steady-state PK parameters
timeFrame: Through study completion, an average of 3 years
measure: 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))
timeFrame: Through study completion, an average of 3 years
measure: Phase I & IIa : Complete response rate (CRR, defined as sCR + CR) assessed according to IMWG criteria
timeFrame: Through study completion, an average of 3 years
measure: Phase I & IIa : Very good or better partial response rate assessed according to IMWG criteria (≥ VGPR rate, defined as VGPR + sCR + CR)
timeFrame: Through study completion, an average of 3 years
measure: Phase I & IIa : Time to response (TTR) assessed according to IMWG criteria
timeFrame: Through study completion, an average of 3 years
measure: Phase I & IIa : Duration of response (DOR) assessed according to IMWG criteria
timeFrame: Through study completion, an average of 3 years
measure: Phase I & IIa : Progression-free survival (PFS) assessed according to IMWG criteria
timeFrame: Through study completion, an average of 3 years
measure: Phase I & IIa : Overall survival (OS)
timeFrame: Through study completion, an average of 3 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hosptital
state: Henan
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Renji Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Hangzhou
country: China
facility: The First Affiliated Hospital，Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: