A Study to Evaluate HMPL-306 in Patients With IDH1or IDH2-mutated Acute Myeloid Leukemia

NCT06387069 | Recruiting Phase 3 DMC

• 1 other identifier: 2023-306-00CH1
• Study Type: interventional
• Target: 316
• Locations: 1 country
• Sites: 53

Brief Summary

This study is a multicenter, randomized, open-label, phase III clinical study (RAPHAEL) to evaluate the efficacy, safety, and PK of HMPL-306 versus salvage chemotherapy in patients with R/R AML harboring IDH1 and IDH2 mutations.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia; IDH

Outcome Measures

Primary Outcomes (1)

• OS

  Overall survival (OS)

  Up to approximately 33 months

Secondary Outcomes (12)

• CR rate

  Up to approximately 33 months

• CR + CRh rate

  Up to approximately 33 months

• CR + CRi + CRh rate

  Up to approximately 33 months

• Assessments for PK (pharmacokinetics)

  Day1 of cycle 1, 3, 5 (each cycle is 28 days)，up to approximately 33 months

• Assessments for PK (pharmacokinetics)

  Day1 of cycle 1, 3, 5 (each cycle is 28 days)，up to approximately 33 months

Study Arms (2)

HMPL-306 arm

EXPERIMENTAL

HMPL-306

Drug: HMPL-306 Regimen

Salvage treatment arm

ACTIVE COMPARATOR

Salvage treatment

Drug: Salvage Chemotherapy Regimen

Interventions

HMPL-306 Regimen DRUG

Patients will receive HMPL-306 monotherapy: HMPL-306 PO at 250 mg QD (C1) + 150 mg QD (starting from C2), 28 days as a cycle.

HMPL-306 arm

Salvage Chemotherapy Regimen DRUG

Patients in this regimen will receive treatment with one of the following regimens, and the regimen will be selected by the investigator based on the patient's condition: * EA±Mitox regimen: etoposide injection 100 mg/m2, cytarabine injection 100-150 mg/m2, mitoxantrone injection 8 mg/m2 QD IV for 5 consecutive days (Days 1-5). * FLAG ± Ida regimen: G-CSF injection 300 mcg/m2 QD SC for 5 consecutive days (Days 1-5); fludarabine injection 30 mg/m2 QD IV for 5 consecutive days (Days 2-6); cytarabine injection 1000-2000 mg/m2 QD IV for 5 consecutive days (Days 2-6); idarubicin injection 10 mg/m2 QD IV for 3 consecutive days (Days 2-4). * LoDAC: -Cytarabine Injection 20 mg every 12 hours, subcutaneous or IV for 10 consecutive days (Days 1-10). * Azacitidine: Azacitidine Injection 75 mg/m2, QD, subcutaneous or IV for 7 consecutive days (Days 1-7).

Salvage treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have signed the ICF;
• Be able to follow the requirements of study protocol;
• Age ≥18 years;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 2;
• Cohort 1: Patients with R/R primary AML harboring IDH1-R132 site mutation \[WHO 2022 Classification Criteria for Myeloid Neoplasms and Acute Leukemia, with the exception of APL (AML-M3) and extramedullary recurrence of leukemia alone without bone marrow involvement\]; Cohort 2: Patients with R/R primary AML harboring IDH2-R140/R172 mutations \[WHO 2022 Classification Criteria for Myeloid Neoplasms and Acute Leukemia, with the exception of APL (AML-M3) and recurrence of extramedullary leukemia alone without bone marrow involvement\]. A patient with both IDH1 and IDH2 mutations will be included in Cohort 2 (IDH2 mutation group);
• Agree to undergo bone marrow aspiration and/or biopsy before and during treatment;
• Be willing to complete QoL assessments at specified time points during study treatment and after treatment discontinuation;
• Female patients of childbearing potential must agree to use highly effective contraceptive methods during the study and within 30 days after discontinuation of the study drug (the time limit of contraception for the chemotherapy group needs to be extended to 6 months after the last dose) (see Appendix 9 (contraception requirements) for more information), and agree not to donate eggs (oocytes) for reproductive purposes during this period; patients must not be lactating and must have a negative pregnancy test (if of childbearing potential);
• Male patients with female partners of childbearing potential must use condoms during intercourse and avoid donating or freezing sperm during the study and within 30 days after discontinuation of the study drug (the time limit of contraception for the chemotherapy group needs to be extended to 6 months after the last dose).
• Predicted survival greater than 12 weeks as assessed by the investigator.

You may not qualify if:

• Patients who meet any of the following criteria must be excluded:
• Patients who received prior treatment with IDH1 inhibitors, IDH2 inhibitors, or IDH1/IDH2 dual target inhibitors;
• Patients with known RAS or FLT3 hotspot mutations (patients who have test results definitely switched to negative at the time of enrollment can be enrolled);
• Hotspot mutations include:
• KRAS mutations: G12 or G13 (exon 2); Q61 (exon 3) NRAS mutations: G12 or G13 (exon 2); Q61 (exon 3) FLT3 mutations: ITD; TKD (D835 or I836)
• Inadequate organ function, as defined below:
• Serum total bilirubin (TBIL) higher than 1.5 times the upper limit of normal (ULN), excluding the following patients:
• \- Patients with Gilbert's disease, with normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and serum TBIL ≤ 3 × ULN.
• AST or ALT \> 2.5 × ULN (if leukemia invades the liver, patients with AST and ALT levels ≤ 5 × ULN can be enrolled);
• Estimated creatinine clearance by Cockcroft-Gault formula \< 50 mL/min or creatinine \> 1.5 × ULN;
• International Normalized Ratio (INR) \> 1.5 × ULN or activated partial thromboplastin time (aPTT) \> 1.5 × ULN, except for patients who are receiving anticoagulant therapy;
• Blood amylase \> 1.5 × ULN and assessed to be clinically significant by the investigator;
• Current known history of liver disease, including cirrhosis, alcoholic liver disease, active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV):
• Patients who are positive for serum hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) are required to undergo HBV deoxyribonucleic acid (DNA) testing, and patients with HBV DNA test results that are either negative or below the lower limit of normal at the site can be enrolled;
• Patients with positive HCV serology may be enrolled only if the HCV ribonucleic acid (RNA) test is negative or below the lower limit of normal at the site;

Sponsors & Collaborators

• Hutchmed: lead

Study Sites (53)

Anhui Provincial Hospital（The First Affiliated Hospital of U STC）

Hefei, Anhui, 230001, China

RECRUITING

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

RECRUITING

The Second Hospital of Anhui Medical University

Hefei, Anhui, 230601, China

RECRUITING

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, China

RECRUITING

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

The First Affilated Hospital of Fujian Medical University

Fuzhou, Fujian, 350005, China

RECRUITING

Quanzhou First Hospital Affiliated to Fujian Medical University

Quanzhou, Fujian, 362000, China

RECRUITING

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Guangzhou First People's Hospital

Guangzhou, Guangdong, 510180, China

RECRUITING

Nanfang Hospital，Southern Medical University

Guanzhou, Guangdong, 510515, China

RECRUITING

Shenzhen Second People's Hospital

Shenzhen, Guangdong, 518035, China

RECRUITING

Affiliated Hospital of Guangdong Medical University

Zhanjiang, Guangdong, 524001, China

RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China

RECRUITING

Guizhou Provincial People's Hospital

Guiyang, Guizhou, 550002, China

RECRUITING

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, 550004, China

RECRUITING

Affiliated Hospital of Zunyi Medical Univercity

Zunyi, Guizhou, 563003, China

RECRUITING

Baoding NO.1 Central Hospital

Baoding, Hebei, 071000, China

RECRUITING

Affiliated Hospital of Chengde Medical University

Chengde, Hebei, 067000, China

RECRUITING

The Second Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050000, China

RECRUITING

Harbin First Hospital

Harbin, Heilongjiang, 150010, China

RECRUITING

The First Affilated Hospital of Henan University of Science & Technology

Luoyang, Henan, 471003, China

RECRUITING

The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

RECRUITING

Wuhan Union Hospital of China

Wuhan, Hubei, 430022, China

RECRUITING

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

RECRUITING

People's Hospital of Hunan Province

Changsha, Hunan, 410005, China

RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, 410008, China

RECRUITING

The Third Xiangya Hospital of Central South University

Changsha, Hunan, 410013, China

RECRUITING

Nanjing Drum Tower Hospital

Nanjing, Jiangsu, 210008, China

RECRUITING

Jiangsu Province Hospital

Nanjing, Jiangsu, 210029, China

RECRUITING

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, 215006, China

RECRUITING

Wuxi People's Hospital

Wuxi, Jiangsu, 214023, China

RECRUITING

The Affiliated Hospital of Xuzhou Medical University

Xuzhou, Jiangsu, 221004, China

RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

RECRUITING

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

RECRUITING

Shengjing Hospital of China Medical University

Shenyang, Liaoning, 110004, China

RECRUITING

The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hosiptal)

Xi'an, Shaanxi, 710004, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

RECRUITING

Ruijin Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

RECRUITING

Tongji Hospital of Tongji University

Shanghai, Shanghai Municipality, 200065, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China

RECRUITING

The second people's hospital of Yibin

Yibin, Sichuan, 644000, China

RECRUITING

XinjiangUiger Municipal People's Hospital

Ürümqi, Xinjiang, 830001, China

RECRUITING

The First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650032, China

RECRUITING

The First People's Hospital of Yunnan Province

Kunming, Yunnan, 650032, China

RECRUITING

The First Affiliated Hospital, Zhejiang University

Hangzhou, Zhejiang, 310003, China

RECRUITING

The First Affiliated Hospital of WMU

Wenzhou, Zhejiang, 325000, China

RECRUITING

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Tianjin, 300020, China

RECRUITING

Tianjin People's Hospital

Tianjin, 300121, China

RECRUITING

Related Publications (1)

• Hu L, Wei X, Zhao W, Hu Y, Li J, Dong Y, Gong T, Zhang X, Xu Y, Zhang Y, Xu C, Zhang C, Cai Z, Jing H, Mi R, Wu W, He W, Wang H, Tang Q, Jiang Z, Liu H, Chen G, Sun J, Chen J, Yan S, Yan H, Wangwu J, Zhong Z, Wang L, Fan S, Shi M, Su W, Huang X. HMPL-306 in relapsed or refractory IDH1- and/or IDH2-mutated acute myeloid leukemia: A phase 1 study. Med. 2025 Jun 13;6(6):100575. doi: 10.1016/j.medj.2025.100575. Epub 2025 Jan 31.

  PMID: 39892383 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Xiaojun Huang, Doctor

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Erin Lou, Doctor

CONTACT

+86 21 2067 1942; erinl@hutch-med.com

Yu Wang, Bachelor

CONTACT

(+86) 18058125909; yuwang@hutch-med.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 16, 2024
• First Posted: April 26, 2024
• Study Start: April 26, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): September 30, 2029
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (53)