Clinical Study of HMPL-689 for Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma

A Multi-center, Single-arm, Open-label Clinical Study to Evaluate the Efficacy and Safety of HMPL-689 in Patients With Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma

A Multi-center, Single-arm, Open-label Clinical Study to Evaluate the Efficacy and Safety of HMPL-689 in Patients with Relapsed/Refractory Marginal Zone Lymphoma (MZL) and Follicular Lymphoma (FL)

Study Overview

• Status: Completed
• Conditions: Follicular Lymphoma; Marginal Zone Lymphoma
• Intervention / Treatment: Drug: HMPL-689

Detailed Description

This is a multi-center, single-arm, open-label clinical study to evaluate the oral therapy with HMPL-689 in patients with relapsed / refractory MZL and FL. Relapse / refractory is defined as such a situation when a patient has not achieved response (CR or PR) after the latest line of systemic treatment, or has disease progress (PD) or relapse after achieving response. Two (2) cohorts of patients will be enrolled in this study:

Cohort 1: approximately 81 patients with histologically confirmed MZL

Cohort 2: approximately 104 patients with histologically confirmed FL (pathological grade 1-3a)

All patients are to receive monotherapy of HMPL-689 30 mg once a day (QD) continuously in 28-day treatment cycles until PD / recurrence, patient death, intolerable toxicity, initiation of other antitumor therapy, the patient unable to further benefit from the study treatment as judged by the investigators, the patient or his/her legal representative's request to withdraw from the clinical study treatment, the patient lost to follow-up or end of the study, whichever comes first.

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Beijing Tongren Hospital, Capital Medical University
    • Beijing, Beijing, China, 100020
      • Beijing Chao-yang Hospital, Capital Medical University
    • Beijing, Beijing, China
      • Beijing GoBroad Boren Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400030
      • Chongqing University Cancer Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350014
      • Fujian Cancer Hospital
    • Xiamen, Fujian, China, 361001
      • The first affiliated hospital of xiamen university
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital, Southern Medical University
    • Shantou, Guangdong, China, 515031
      • Cancer Hospital of Shantou University Medical College
    • Zhuhai, Guangdong, China
      • The Fifth Affiliated Hospital of Sun Yat-sen University
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • Guangxi Medical University Affiliated Tumor Hospital
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
  • Hebei
    • Chengde, Hebei, China
      • Affiliated Hospital of Chengde Medical University
    • Shijia Zhuang, Hebei, China
      • The Fourth Hospital of Hebei Medical University
    • Xingtai, Hebei, China
      • Xingtai People's Hospital
  • Heilongjiang
    • Ha'erbin, Heilongjiang, China
      • The First Affiliated Hospital of Harbin Medical University
    • Ha'erbin, Heilongjiang, China
      • The First Hospital of Harbin
  • Henan
    • Luoyang, Henan, China
      • The First Affiliated Hospital of Henan University of Science And Technology
    • Puyang, Henan, China, 410900
      • Puyang Oilfield General Hospital
    • Zhengzhou, Henan, China, 450052
      • The first affiliated hospital of Zhengzhou university
    • Zhengzhou, Henan, China, 450003
      • Henan Provincial People's Hospital
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430061
      • People's Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China
      • The second Xiangya hospital of central south university
    • Changsha, Hunan, China, 410013
      • Hunan Cancer Hospital
    • Huaihua, Hunan, China
      • The Second People's Hospital of Huaihua
    • Yongzhou, Hunan, China, 425006
      • The Central Hospital of Yongzhou
  • Jiangsu
    • Nantong, Jiangsu, China, 226001
      • The First People's Hospital of Nantong
    • Suzhou, Jiangsu, China
      • The Second Affiliated Hospital of Suzhou University
  • Jiangxi
    • Gannan, Jiangxi, China
      • The First Affiliated Hospital of Gannan Medical University
    • Ganzhou, Jiangxi, China
      • Ganzhou People's Hospital
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of NanChang University
    • Nanchang, Jiangxi, China
      • Jiangxi Provincial Cancer Hospital
  • Jilin
    • Changchun, Jilin, China, 130000
      • The First Hospital of Jilin University
  • Liaoning
    • Jinzhou, Liaoning, China
      • The First Affiliated Hospital of Jinzhou Medical University
    • Shengyang, Liaoning, China
      • Shengjing Hospital Of China Medical University
  • Shandong
    • Binzhou, Shandong, China
      • Affiliated Hospital of Binzhou Medical University
    • Jinan, Shandong, China
      • Jinan Central Hospital
    • Jinan, Shandong, China
      • Qilu Hospital of Shandong University
    • Qingdao, Shandong, China, 266000
      • The Affiliated Hospital of Qingdao University
  • Shanghai
    • Shanghai, Shanghai, China, 200433
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200092
      • Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine
    • Shanghai, Shanghai, China
      • Shanghai East Hospital, Tongji University School of Medicine
  • Shanxi
    • Taiyuan, Shanxi, China
      • The First Hospital of Shanxi Medical University
    • Taiyuan, Shanxi, China, 30002
      • Shanxi Bethune Hospital
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital Sichuan University
    • Nanchong, Sichuan, China, 637000
      • Affiliated Hospital of North Sichuan Medical College
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin Medical University Cancer Institute and Hospital
  • Xinjiang
    • Ürümqi, Xinjiang, China, 830000
      • Cancer Hospital affiliated to Xinjiang Medical University
  • Yunnan
    • Kunming, Yunnan, China
      • Yunnan Cancer Hospital
    • Kunming, Yunnan, China
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
    • Hangzhou, Zhejiang, China, 310003
      • The first Affiliated Hospital, Zhejiang University School of Medicine
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥18 years;
2. Patients with relapsed/refractory marginal zone lymphoma or follicular lymphoma
3. Eastern Cooperative Oncology Group (ECOG) Performance Status score 0-2;
4. At least one measurable lesion by computerised tomography (CT) / magnetic resonance imaging (MRI) (the longest diameter of nodal lesion > 1.5 cm or extranodal lesion > 1 cm);
5. Expected survival of more than 12 weeks;

Exclusion Criteria:

1. Having lymphoma with central nervous system (CNS) or cerebral pia mater invasion;
2. Known histologic transformation to aggressive lymphomas such as diffuse large B-cell lymphoma (DLBCL);
3. Prior use of any phosphatidylinositol 3-kinase (PI3K) inhibitor;
4. Inadequate organ function of liver and kidney;
5. Currently known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV);
6. Having received systemic antitumor therapy or radiotherapy within 4 weeks prior to the first dose of the investigational product;
7. Toxicity of previous antitumor therapy not recovered to CTCAE grade ≤ 1, except alopecia, prior to the first dose of the investigational product;
8. Complicated with uncontrolled systemic infection requiring intravenous antibiotic treatment;
9. Pregnant (positive serum pregnancy test) or lactating women;
10. Any other disease, metabolic abnormality, physical examination abnormality or clinically significant laboratory test abnormality, one disease or state providing a reason to suspect that the subject is not suitable for HMPL-689 at the investigator's discretion, or one condition that will affect interpretation of the study results or bring the subject at high risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relapsed/Refractory MZL and FL; Relapsed/Refractory Marginal Zone Lymphoma and Follicular Lymphoma	Drug: HMPL-689; All patients are to receive monotherapy of HMPL-689 30 mg QD continuously in 28-day treatment cycles.; Other Names: Phosphatidylinositol 3-kinase-δ inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Defined as the proportion of patients with CR or PR	Baseline up to the last patient has completed 12 months after treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response (CR) rate	Defined as the proportion of patients with CR.	Baseline up to the last patient has completed 12 months after treatment.
Progression-free survival (PFS)	Defined as the time from the first dose of HMPL-689 to occurrence of PD or death, whichever comes first.	Baseline up to the last patient has completed 12 months after treatment.
Time to response (TTR)	Defined as the time from the first dose of HMPL-689 to the first objective response.	Baseline up to the last patient has completed 12 months after treatment.
Duration of response (DoR)	Defined as the time from the initial objective response to disease recurrence, progression or death.	Baseline up to the last patient has completed 12 months after treatment.
Overall survival (OS)	Defined as the time from the first dose with HMPL-689 to death from any cause.	Baseline up to the last patient has completed 12 months after treatment.

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Investigators: Principal Investigator: junning Cao, Ph.D, Fudan University; Principal Investigator: Zhiming Li, post-doc, Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Actual): February 29, 2024
• Study Completion (Actual): February 29, 2024

Study Registration Dates

• First Submitted: April 13, 2021
• First Submitted That Met QC Criteria: April 13, 2021
• First Posted (Actual): April 19, 2021

Study Record Updates

• Last Update Posted (Actual): April 6, 2025
• Last Update Submitted That Met QC Criteria: April 3, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Follicular Lymphoma; Marginal Zone Lymphoma; Phosphatidylinositol 3-kinase inhibitor
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma; Lymphoma, Follicular; Lymphoma, B-Cell, Marginal Zone
• Other Study ID Numbers: 2020-689-00CH3

Drug and device information, study documents

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