ICP-248 in Combination With Azacitidine for the Treatment in Patients With Myeloid Malignancies

Phase 1

Recruiting

• Conditions: Acute Myelogenous Leukemia; Myelodysplastic Syndromes (MDS)
• Interventions: Drug: ICP-248; Drug: Azacitidine

• Registration Number: NCT06656494
• Lead Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

Brief Summary

Evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ICP-248 in combination with azacitidine in patients with acute myelogenous leukemia and Myelodysplastic Syndromes.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-10-21
• Study First Submitted QC: 2024-10-22
• Study First Posted: 2024-10-24
• Study Start: 2024-12-18
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-03
• Last Update Posted: 2025-07-08
• Primary Completion: 2027-06
• Study Completion: 2028-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 206

Inclusion Criteria

• Eligible subjects must meet all of the following criteria:

  1. Subject must have confirmation of diagnosis of AML (except for acute promyelocytic leukemia [APL]) or MDS per 2016 World Health Organization (WHO) criteria.

  2. For AML (except for APL) cohort:

     1. Previously treated relapsed/refractory AML subjects

     2. Treatment-naïve AML subjects should be:

        • 60 years of age OR ≥18 years and <60 years will be eligible if the subject has at least one of the following co-morbidities, which make the subject unfit for intensive chemotherapy

  3. For MDS cohort:

     Adult TN MDS and R/R MDS: revised International Prognostic Scoring System (IPSS-R) score > 3 and bone marrow blasts ≥ 5%.

  4. Subject must have a projected life expectancy of at least 12 weeks.

  5. Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft-Gault formula.

  6. Subject must have adequate liver function

Exclusion Criteria

1. R/R AML or R/R MDS with no response or intolerance to post azacitidine or BCL-2i.
2. Subject has acute promyelocytic leukemia (French-American-British Class M3 AML) or AML with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1.
3. Subject has known central nervous system (CNS) leukemia.
4. Suggest patients with active hepatitis B or C virus infection
5. History of immunodeficiency, including a positive human immunodeficiency virus (HIV) antibody test.
6. Subjects have another active malignancy within the past 2 years before study entry, except for curatively treated.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ICP-248 in combination with azacitidine	ICP-248	-
ICP-248 in combination with azacitidine	Azacitidine	-

Primary Outcome Measures

Name	Time	Method
MDS cohort：mOR rate, including CR, mCR, and PR, assessed by Investigator at any time point during the study per revised IWG 2006 MDS Criteria.	2.5 years
Incidence, type, and severity of dose-limiting toxicity (DLT).	2.5 years
Recommended phase II dose (RP2D) and/or maximum tolerated dose (MTD).	2.5 years
The incidence, nature, and severity of adverse events (AEs) as assessed per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) criteria.	2.5 years
AML cohort:Composite complete remission rate by Investigator per ELN 2017 criteria.	2.5 years
AML cohort：Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria.	2.5 years

Secondary Outcome Measures

Name	Time	Method
Area under the curve (AUC) of ICP-248.	2.5 years
Trough concentration(Ctrough) of ICP-248.	2.5 years
AML cohort：Partial Response (PR) by investigator per ELN 2017 criteria.	2.5 years
AML cohort：Morphologic leukemia-free state (MLFS) by investigator per ELN 2017 criteria.	2.5 years
AML cohort：Composite complete remission rate: The proportion of subjects with complete remission (CR) and CR with incomplete hematologic recovery (CRi) by Investigator per European Leukemia Net (ELN) 2017 criteria.	2.5 years
AML cohort：Composite complete remission rate by completion of cycle 2 by Investigator per ELN 2017 criteria.	2.5 years
AML cohort：Overall survival (OS) by investigator per ELN 2017 criteria.	2.5 years
Maximum concentration (Cmax)of ICP-248.	2.5 years
The incidence, nature, and severity of adverse events (AEs) as assessed per NCI-CTCAE v5.0 criteria.	2.5 years
Time of maximum observed plasma(Tmax)of ICP-248.	2.5 years
Apparent clearance (CL/F) of ICP-248.	2.5 years
AML cohort：Duration of Response (DOR) by investigator per ELN 2017 criteria.	2.5 years
AML cohort：Relapse-free Survival (RFS) by investigator per ELN 2017 criteria.	2.5 years
AML cohort：Event-free Survival (EFS) by investigator per ELN 2017 criteria.	2.5 years
MDS cohort：Modified overall response (mOR) rate, including CR, marrow complete response (mCR), and PR, assessed by Investigator at any time point during the study per revised International Working Group (IWG) 2006 MDS Criteria	2.5 years
MDS cohort：Complete remission(CR) rate by Investigator per revised IWG 2006 MDS Criteria	2.5 years
MDS cohort：Event-free survival (EFS) by Investigator per revised IWG 2006 MDS Criteria	2.5 years
MDS cohort：Duration of modified overall response (DmOR) by Investigator per revised IWG 2006 MDS Criteria	2.5 years
MDS cohort：Overall survival(OS) by Investigator per revised IWG 2006 MDS Criteria	2.5 years
MDS cohort：Marrow complete response (mCR) rate by Investigator per revised IWG 2006 MDS Criteria	2.5 years

Trial Locations

Locations (6)

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China

The First Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China

The First Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

Tianjin People's Hospital; 🇨🇳 Tianjin, Tianjin, China

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital, Zhejiang University School of Medicine; 🇨🇳 Hangzhou, Zhejiang, China