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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Relapsed and/or Refractory Multiple Myeloma
• Intervention / Treatment: Drug: ICP-490; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: April Huang; Phone Number: 010-66609723; Email: April.huang@innocarepharma.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • Peking University People's Hospital
      • Contact: Xiaojun Huang, PhD
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Not yet recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Yang Liang
  • Henan
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • Henan Cancer Hosptital
      • Contact: Baijun Fang
  • Liaoning
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • Shengjing Hospital of China Medical University
      • Contact: Aijun Liao, PhD
  • Shanghai
    • Shanghai, Shanghai, China
      • Not yet recruiting
      • Renji Hospital, Shanghai Jiao Tong University School of Medicine
      • Contact: Lijing Shen
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Not yet recruiting
      • The First Affiliated Hospital，Zhejiang University School of Medicine
      • Contact: Zhen Cai, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ICP-490	Drug: ICP-490; Several dose groups of ICP-490 are planned for the dose exploration.
Experimental: ICP-490 in combination with Dexamethasone	Drug: ICP-490; Several dose groups of ICP-490 are planned for the dose exploration.; Drug: Dexamethasone; Oral Dexamethasone is administered on Days 1, 8, 15, and 22 of each 28-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Through study completion, an average of 3 years
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.	Through study completion, an average of 3 years
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%).	Through study completion, an average of 3 years
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.	Through study completion, an average of 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration (Cmax)	Maximum concentration (Cmax) will be calculated through multiple plasma concentrations drawn from the patients after administration.	Through study completion, an average of 3 years
Time to maximum concentration (Tmax)	Time to maximum concentration (Tmax) will be calculated through multiple plasma concentrations drawn from the patients after administration.	Through study completion, an average of 3 years
Half-life (T1/2)	Half-life (T1/2) will be calculated through multiple plasma concentrations drawn from the patients after administration.	Through study completion, an average of 3 years
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.	Through study completion, an average of 3 years
Apparent clearance (CL/F)	Apparent clearance (CL/F) will be calculated through multiple plasma concentrations drawn from the patients after administration.	Through study completion, an average of 3 years
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.	Through study completion, an average of 3 years
Steady-state PK parameters	Steady-state PK parameters will be calculated through multiple plasma concentrations drawn from the patients after administration.	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))	Disease response will be assessed according to the 2016 IMWG response criteria.	Through study completion, an average of 3 years
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.	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)	Disease response will be assessed according to the 2016 IMWG response criteria.	Through study completion, an average of 3 years
Phase I & IIa : Time to response (TTR) assessed according to IMWG criteria	Disease response will be assessed according to the 2016 IMWG response criteria	Through study completion, an average of 3 years
Phase I & IIa : Duration of response (DOR) assessed according to IMWG criteria	Disease response will be assessed according to the 2016 IMWG response criteria	Through study completion, an average of 3 years
Phase I & IIa : Progression-free survival (PFS) assessed according to IMWG criteria	Disease response will be assessed according to the 2016 IMWG response criteria	Through study completion, an average of 3 years
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.	Through study completion, an average of 3 years

Collaborators and Investigators

• Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Estimated): July 30, 2025
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 30, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 9, 2024
• Last Update Submitted That Met QC Criteria: April 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: ICP-CL-01101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No