Study of HMPL-760 Plus R-GemOx Versus Placebo Plus R-GemOx in Relapsed/Refractory DLBCL

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

The goal of this study is to evaluate the efficacy 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 (R/R DLBCL).

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsed/Refractory Diffuse Large B-Cell Lymphoma
• Intervention / Treatment: Drug: HMPL-760 planned dose 1; Drug: R-GemOx; Drug: HMPL-760 placebo planned dose 1; Drug: HMPL-760 planned dose 2; Drug: HMPL-760 placebo planned dose 2

Detailed Description

A Phase II Randomized, 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 (R/R DLBCL). The study phases include screening period, treatment period, safety observation period, PFS follow-up period, and OS follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
  • Guangxi
    • Nanning, Guangxi, China
      • Guangxi Medical University Cancer Hospital
  • Hebei
    • Wuhan, Hebei, China
      • Wuhan Union Hospital of China
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Medical University Cancer Hospital
    • Harbin, Heilongjiang, China
      • Harbin First Hospital
  • Henan
    • Zhengzhou, Henan, China
      • Henan Cancer Hospital
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China
      • Jiangxi Cancer Hospital
    • Nanchang, Jiangxi, China
      • The First Affiliated Hospital of Nanchang University
  • Liaoning
    • Shenyang, Liaoning, China
      • Shengjing Hospital of China Medical University
  • Shandong
    • Jinan, Shandong, China
      • Shandong Cancer Hospital & Institute
  • Shanghai
    • Shanghai, Shanghai, China
      • Ruijin Hospital, Shanghai Jiaotong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China
      • Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Sign the Informed consent form(ICF) and be able to follow the requirements of study protocol;
2. Age ≥18 years;
3. Eastern Cooperative Oncology Group (ECOG) performance status 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. Toxicities from prior anticancer therapy not resolved to Grade ≤ 1 (except for alopecia and decreased appetite);
8. Clinically significant active infection;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen; Group A: Patients will receive HMPL-760 planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.	Drug: HMPL-760 planned dose 1; HMPL-760 planned dose 1 daily (QD) orally; Drug: R-GemOx; R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.; Other Names: Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection
Placebo Comparator: Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen; Patients will receive HMPL-760 placebo planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.	Drug: R-GemOx; R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.; Other Names: Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection; Drug: HMPL-760 placebo planned dose 1; HMPL-760 placebo planned dose 1 daily (QD) orally
Experimental: Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen; Patients will receive HMPL-760 planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.	Drug: R-GemOx; R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.; Other Names: Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection; Drug: HMPL-760 planned dose 2; HMPL-760 planned dose 2 daily (QD) orally
Placebo Comparator: Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen; Patients will receive HMPL-760 placebo planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.	Drug: R-GemOx; R-GemOx regimen includes Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection. R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m^2 ivgtt is given, followed by oxaliplatin 100 mg/m^2 ivgtt on day 2 of each cycle.; Other Names: Rituximab Injection, Gemcitabine Hydrochloride for Injection, Gemcitabine Hydrochloride for Injection; Drug: HMPL-760 placebo planned dose 2; HMPL-760 placebo planned dose 2 daily (QD) orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014).	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate (ORR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR), as assessed by investigator.	Up to approximately 2 years
Complete response (CR) rate	Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR), as assessed by investigator.	Up to approximately 2 years
Duration of response (DoR)	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, as assessed by investigator.	Up to approximately 2 years
Clinical benefit rate (CBR)	Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD).	Up to approximately 2 years
Time to response (TTR)	Time To Response (TTR) is defined as the time from the start of treatment to the first objective response rate (ORR), as assessed by investigator.	Up to approximately 2 years
Overall survival (OS)	Overall Survival (OS) is defined as the time from randomization to death due to any cause.	Up to approximately 2 years
Safety Endpoints of adverse events	Incidence and severity of treatment-emergent adverse events (TEAEs), incidence of serious adverse events (SAEs), 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 5.0 (NCI CTCAE 5.0).	Up to approximately 2 years
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx	Trough plasma concentration (Ctrough) of drug	At the end of Cycle 7 (each cycle is 21 days)
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx	Maximum observed concentration, occurring at time Tmax at steady-state (Cmax,ss) of drug	At the end of Cycle 7 (each cycle is 21 days)
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx	Time of maximum observed concentration at steady-state(Tmax,ss) of drug	At the end of Cycle 7 (each cycle is 21 days)
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx	The partial area from dosing time to dosing time plus Tau at steady-state (AUCss) of drug	At the end of Cycle 7 (each cycle is 21 days)
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx	Apparent clearance at steady-state (CLss/F) of drug (if applicable)	At the end of Cycle 7 (each cycle is 21 days)
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx	Apparent volume of distribution at steady-state (Vz,ss/F) of drug (if applicable)	At the end of Cycle 7 (each cycle is 21 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker assessment	To evaluate the correlation between potential biomarkers and the prognosis of patients treated with this regimen. Tumor tissue or blood samples will be examined to detect the gene expression of MYD88.	Up to approximately 2 years
Metabolite analysis of HMPL-760 in combination with R-GemOx	Analysis metabolite of HMPL-760 in combination with R-GemOx	At the end of Cycle 7 (each cycle is 21 days)

Collaborators and Investigators

• Sponsor: Hutchmed
• Investigators: Principal Investigator: Weili Zhao, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2024
• Primary Completion (Estimated): May 12, 2026
• Study Completion (Estimated): November 12, 2026

Study Registration Dates

• First Submitted: September 8, 2024
• First Submitted That Met QC Criteria: September 14, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

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

More Information

Terms related to this study

• Keywords: R/R DLBCL; R-GemOx; HMPL-760
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Gemcitabine
• Other Study ID Numbers: 2024-760-00CH1

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
• product manufactured in and exported from the U.S.: No