A Phase III Study of HMPL-760 Plus R-GemOx VS Placebo Plus R-GemOx in Relapsed/Refractory DLBCL

March 27, 2026 updated by: Hutchmed

A Phase III Randomized, Double-Blind, Positive Controlled Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of HMPL-760 in Combination With R-GemOx Versus Placebo in Combination With R-GemOx in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

This is a Phase III randomized, double-blind, positive controlled study to evaluate the efficacy, safety, and pharmacokinetics of HMPL-760 in combination with R-GemOx versus placebo in combination with R-GemOx in patients with R/R DLBCL.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study phases include screening period, treatment period, safety observation period, PFS follow-up period, and OS follow-up period.

The target population of this study includes patients with DLBCL who are relapsed or refractory.

Study Type

Interventional

Enrollment (Estimated)

240

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Baoding, China
        • Not yet recruiting
        • Baoding NO.1 Central Hospital
        • Contact:
        • Principal Investigator:
          • Haiying Yao
      • Beijing, China
        • Not yet recruiting
        • Beijing Tongren Hospital, Capital Medical University
        • Principal Investigator:
          • Liang Wang
        • Contact:
      • Beijing, China
        • Not yet recruiting
        • Beijing GoBroad Hospital
        • Principal Investigator:
          • Kai Hu
        • Contact:
      • Bengbu, China
        • Not yet recruiting
        • The First Affiliated Hospital of Bengbu Medical College
        • Contact:
        • Principal Investigator:
          • Yanli Yang
      • Changchun, China
        • Not yet recruiting
        • The First Hospital of Jilin University
        • Principal Investigator:
          • Ou Bai
        • Contact:
      • Changsha, China
        • Not yet recruiting
        • Hunan Cancer Hospital
        • Principal Investigator:
          • Hui Zhou
        • Contact:
      • Changsha, China
        • Not yet recruiting
        • The Second Xiangya Hospital of Central South University
        • Principal Investigator:
          • Hongling Peng
        • Contact:
      • Changsha, China
        • Not yet recruiting
        • People's Hospital of Hunan Province
        • Contact:
        • Principal Investigator:
          • Can Liu
      • Chengdu, China
        • Not yet recruiting
        • West China Hospital of Sichuan University
        • Principal Investigator:
          • Liqun Zou
        • Contact:
      • Chengdu, China
        • Not yet recruiting
        • Sichuan Provincial People's Hospital
        • Contact:
        • Principal Investigator:
          • xiaobing huang
      • Chongqing, China
        • Not yet recruiting
        • Chongqing University Cancer Hospital
        • Principal Investigator:
          • Yao Liu
        • Contact:
      • Fujian, China
        • Not yet recruiting
        • Quanzhou First Hospital.Fujian
        • Contact:
        • Principal Investigator:
          • Xiongpeng Zhu
      • Fuzhou, China
        • Not yet recruiting
        • Fujian Medical University Union Hospital
        • Principal Investigator:
          • Jianzhen Shen
        • Contact:
      • Guangzhou, China
        • Not yet recruiting
        • Sun Yat-sen University Cancer Center
        • Principal Investigator:
          • Zhiming Li
        • Contact:
      • Guangzhou, China
        • Not yet recruiting
        • ZhuJiang Hospital of Southern Medical University（The Second Clinical Medical College）
        • Principal Investigator:
          • Yuhua Li
        • Contact:
      • Guiyang, China
        • Not yet recruiting
        • The Affiliated Hospital of Guizhou Medical University
        • Principal Investigator:
          • Yan Zhang
        • Contact:
      • Hangzhou, China
        • Not yet recruiting
        • Zhejiang Cancer Hospital
        • Principal Investigator:
          • Haiyan Yang
        • Contact:
      • Hangzhou, China
        • Not yet recruiting
        • The First Affiliated Hospital, Zhejiang University
        • Principal Investigator:
          • Zhen Cai
        • Contact:
      • Harbin, China
        • Not yet recruiting
        • Harbin Medical University Cancer Hospital
        • Contact:
        • Principal Investigator:
          • Qingyuan Zhang
      • Hefei, China
        • Not yet recruiting
        • The Second Affiliated Hospital of Anhui Medical University
        • Contact:
        • Principal Investigator:
          • Zhimin Zhai
      • Jinan, China
        • Not yet recruiting
        • Qilu Hospital of Shandong University
        • Contact:
        • Principal Investigator:
          • Shuqian Xu
      • Jinan, China
        • Not yet recruiting
        • Shandong Cancer Hospital & Institute
        • Principal Investigator:
          • Zengjun Li
        • Contact:
      • Nanchang, China
        • Not yet recruiting
        • Jiangxi Cancer Hospital
        • Principal Investigator:
          • Yan Huang
        • Contact:
      • Nanjing, China
        • Not yet recruiting
        • Jiangsu Cancer Hospital
        • Principal Investigator:
          • Yan Zhang
        • Contact:
      • Nanning, China
        • Not yet recruiting
        • The First Affiliated Hospital of Guangxi Medical University
        • Principal Investigator:
          • Zhigang Peng
        • Contact:
      • Qingdao, China
        • Not yet recruiting
        • The Affiliated Hospital of Qingdao University
        • Contact:
        • Principal Investigator:
          • Xia Zhao
      • Shanghai, China
        • Not yet recruiting
        • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
        • Principal Investigator:
          • Weili Zhao
        • Contact:
      • Shanghai, China
        • Not yet recruiting
        • Tongji Hospital of Tongji University
        • Contact:
        • Principal Investigator:
          • Ping Li
      • Shenyang, China
        • Not yet recruiting
        • Shengjing Hospital of China Medical University
        • Principal Investigator:
          • Wei Yang
        • Contact:
      • Taiyuan, China
        • Not yet recruiting
        • Shanxi Provincial Cancer Hospitial
        • Principal Investigator:
          • Liping Su
        • Contact:
      • Tangshan, China
        • Not yet recruiting
        • North China University of Science and Technology Affiliated Hospital
        • Contact:
        • Principal Investigator:
          • Zhenyu Yan
      • Tianjin, China
        • Not yet recruiting
        • Tianjin Medical University Cancer Institute & Hospital
        • Principal Investigator:
          • Zhengzi Qian
        • Contact:
          • Zhengzi Qian
          • Phone Number: 13702031222
          • Email: qzz@163.com
      • Tianjin, China
        • Not yet recruiting
        • Tianjin People's Hospital
        • Contact:
        • Principal Investigator:
          • Xingli Zhao
      • Tianjin, China
        • Recruiting
        • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
        • Principal Investigator:
          • Dehui Zou
        • Contact:
      • Wuhan, China
        • Not yet recruiting
        • Wuhan Union Hospital of China
        • Principal Investigator:
          • Liling Zhang
        • Contact:
      • Wuhan, China
        • Not yet recruiting
        • Hubei Cancer Hospital
        • Principal Investigator:
          • Huijing Wu
        • Contact:
      • Xi'an, China
        • Not yet recruiting
        • The First Affiliated Hospital of Xi'an Jiaotong University
        • Principal Investigator:
          • Pengcheng He
        • Contact:
      • Zhengzhou, China
        • Not yet recruiting
        • Henan Cancer Hospital
        • Principal Investigator:
          • Keshu Zhou
        • Contact:
      • Zhengzhou, China
        • Not yet recruiting
        • The First Affiliated Hospital of Zhengzhou University
        • Contact:
        • Principal Investigator:
          • Xudong Zhang
      • Ürümqi, China
        • Not yet recruiting
        • Cancer Hospital affiliated to Xinjiang Medical University
        • Principal Investigator:
          • Shujuan Wen
        • Contact:
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China
        • Not yet recruiting
        • Fudan University Shanghai Cancer Center
        • Contact:
        • Principal Investigator:
          • Fangfang Lv

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Sign the ICF and be able to follow the requirements of study protocol;
  2. Age ≥18 years;
  3. ECOG performance status score between 0 and 2;
  4. Histopathologically confirmed diagnosis of DLBCL;
  5. The investigator judges that the patient's current condition requires further treatment;
  6. Patients should have at least one bi-dimensionally measurable lesion;
  7. Expected survival is more than 12 weeks;

Exclusion Criteria:

  1. Patients with known primary or secondary central nervous system lymphoma (CNSL) or the presence of clinical symptoms suggestive of CNSL;
  2. Women who are pregnant (positive pregnancy test during the screening period) or breastfeeding;
  3. Organ insufficiency;
  4. Currently known history of liver disease, including cirrhosis, alcoholic liver, known active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV);
  5. History of significant organ bleeding, including gastrointestinal bleeding, hematencephalon, haemoptysis, etc., within 8 weeks prior to the first dose of study drug;
  6. Known risk of bleeding, such as coagulation factor deficiency, vascular hemophilia; or the patient is receiving vitamin K antagonist (warfarin);
  7. The toxic reactions of previous anti-tumor therapy have not recovered to the level of ≤ grade 1 (except for alopecia and decreased appetite and other conditions that have been clearly required in the inclusion and exclusion criteria);
  8. Clinically significant active infection;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: The experimental group
Patients will receive HMPL-760 once daily (QD) orally in combination with R-GemOx regimen in 21-day cycles for a total of 8 cycles. Rituximab 375 mg/m2 IV is given on Day 1 of each cycle, and gemcitabine 1000 mg/m2 IV followed by oxaliplatin 100 mg/m2 IV is given on Day 2 of each cycle.
Drug: HMPL-760
Patients will receive HMPL-760 once daily (QD) orally.
Drug: R-GemOx
R-GemOx regimen in 21-day cycles for a total of 8 cycles. Rituximab 375 mg/m2 IV is given on Day 1 of each cycle, and gemcitabine 1000 mg/m2 IV followed by oxaliplatin 100 mg/m2 IV is given on Day 2 of each cycle.
Other Names:
  • Gemcitabine Hydrochloride for Injection
  • Rituximab Injection
  • Oxaliplatin Injection
Placebo Comparator: The control group
Placebo QD at the same dose as HMPL-760 in the experimental group will be given in the control group, and the combination therapy is the same as in the experimental group.
Drug: R-GemOx
R-GemOx regimen in 21-day cycles for a total of 8 cycles. Rituximab 375 mg/m2 IV is given on Day 1 of each cycle, and gemcitabine 1000 mg/m2 IV followed by oxaliplatin 100 mg/m2 IV is given on Day 2 of each cycle.
Other Names:
  • Gemcitabine Hydrochloride for Injection
  • Rituximab Injection
  • Oxaliplatin Injection
Drug: HMPL-760 Placebo
Patients will receive HMPL-760 placebo once daily (QD) orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: Up to approximately two years
Investigator-assessed progression-free survival (PFS) Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). PFS is defined as the time from randomization to PD or death due to any cause, whichever occurs first.
Up to approximately two years
End of treatment (EOT)
Time Frame: Up to approximately two years
Tumor assessment data will continue to be collected. Tumor assessment data collected after end of treatment (EOT) will be used. Tumor assessment data collected during the study and after EOT will be included in the PFS analysis (treatment policy strategy).
Up to approximately two years
Systemic antitumor therapy
Time Frame: Up to approximately two years
Use of other systemic antitumor therapy before PD or death (in the absence of PD):Tumor assessment after use of other systemic antitumor therapy will not be included in the analysis. For patients using other anti-tumor therapy before PD or death (in absence of PD), PFS will be censored at the last evaluable tumor assessment before the use of other systematic anti-tumor therapy (hypothetical strategy).
Up to approximately two years
Overall survival (OS)
Time Frame: Up to approximately two years
OS is defined as the time from randomization to death due to any cause.
Up to approximately two years
systematic anti-tumor therapy
Time Frame: Up to approximately two years
OS data will continue to be collected after the other systematic anti-tumor therapy, and the OS data collected before and after other systematic anti-tumor therapy will be included in analysis (treatment policy strategy).
Up to approximately two years
Premature withdrawal from study treatment
Time Frame: Up to approximately two years
OS data will continue to be collected after the patient's premature withdrawal from study treatment, and the OS data collected during the study treatment and after EOT will be included in analysis (treatment policy strategy).
Up to approximately two years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Independent review committee (IRC)-assessed PFS
Time Frame: Up to approximately two years
Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014).
Up to approximately two years
IRC- and investigator-assessed objective response rate (ORR)
Time Frame: Up to approximately two years
Objective Response Rate (ORR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR)
Up to approximately two years
IRC- and investigator-assessed complete response rate (CRR)
Time Frame: Up to approximately two years
Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR)
Up to approximately two years
IRC- and investigator-assessed duration of response (DoR)
Time Frame: Up to approximately two years
For patients who reached complete response (CR) or partial response (PR), Duration of Response (DoR) is defined as the time from the first CR or PR until disease progression or death due to any cause, whichever occurs first
Up to approximately two years
IRC- and investigator-assessed clinical benefit rate (CBR)
Time Frame: Up to approximately two years
Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD)
Up to approximately two years
IRC- and investigator-assessed time to response (TTR)
Time Frame: Up to approximately two years
Time To Response (TTR) is defined as the time from the start of treatment to the first objective response rate (ORR)
Up to approximately two years
Safety Endpoints
Time Frame: Up to approximately two years
  • Incidence and severity of treatment-emergent adverse events (TEAEs), incidence of treatment-emergent serious adverse events (TESAEs), incidence of TEAEs leading to permanent discontinuation, dose interruption, and dose reduction, and their correlation to study drug. The severity is determined according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 6.0 (NCI CTCAE 6.0).
  • Changes in laboratory tests, vital signs, 12-lead ECG, etc.
Up to approximately two years
PK characteristics of HMPL-760 in patients with R/R DLBCL when administered in combination with R-GemOx
Time Frame: At the end of Cycle 4 (each cycle is 21 days)]

including but not limited to steady-state plasma concentrations of HMPL-760 pre-dose [trough concentrations (Ctrough)] and post-dose (C1h and C2h); If possible, a population pharmacokinetic (PPK) model can be used to generate PK parameters. If necessary, it can also be combined with other studies for model analysis.

If possible, a population pharmacokinetic (PPK) model can be used to generate PK parameters. If necessary, it can also be combined with other studies for model analysis.
At the end of Cycle 4 (each cycle is 21 days)]

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Biomarker assessment
Time Frame: Up to approximately two years
Detect tumor driver gene mutations in tissue and blood samples, such as MYD88 and CD79B, etc, and explore the relationship between their mutation status and drug efficacy.
Up to approximately two years
To explore the metabolite profile of HMPL-760 in combination with R-GemOx in tumor patients
Time Frame: Up to approximately two years
Human metabolites of HMPL-760 when co-administered with R-GemOx
Up to approximately two years
Pharmacokinetic parameters of gemcitabine and oxaliplatin when combined with HMPL-760
Time Frame: Up to approximately two years
maximum concentration in steady-state (Cmax,ss)
Up to approximately two years
Pharmacokinetic parameters of gemcitabine and oxaliplatin when combined with HMPL-760
Time Frame: Up to approximately two years
time to maximum concentration in steady-state (Tmax,ss)
Up to approximately two years
Pharmacokinetic parameters of gemcitabine and oxaliplatin when combined with HMPL-760
Time Frame: Up to approximately two years
Area Under the Curve at steady state refers to the area under the plasma concentration-time curve during a dosing interval at steady state conditions (AUC,ss)
Up to approximately two years
Pharmacokinetic parameters of gemcitabine and oxaliplatin when combined with HMPL-760
Time Frame: Up to approximately two years
The rate at which the drug is eliminated from the body (CL/F) (if applicable )
Up to approximately two years
Pharmacokinetic parameters of gemcitabine and oxaliplatin when combined with HMPL-760
Time Frame: Up to approximately two years
The distribution volume calculated based on the terminal elimination phase (Vz/F )(if applicable)
Up to approximately two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hutchmed

Investigators

  • Principal Investigator: Weili Zhao, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2026

Primary Completion (Estimated)

April 30, 2028

Study Completion (Estimated)

December 30, 2028

Study Registration Dates

First Submitted

January 28, 2026

First Submitted That Met QC Criteria

February 6, 2026

First Posted (Actual)

February 13, 2026

Study Record Updates

Last Update Posted (Actual)

April 1, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2025-760-00CH1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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