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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| The experimental group | Experimental | 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. |
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| The control group | Placebo Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HMPL-760 | Drug | Patients will receive HMPL-760 once daily (QD) orally. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free survival (PFS) | 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) | 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 | 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) | OS is defined as the time from randomization to death due to any cause. | Up to approximately two years |
| systematic anti-tumor therapy | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Independent review committee (IRC)-assessed PFS | 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Biomarker assessment | 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Dongmei Chen, CPL | Contact | 86-21-20671794 | dongmeic@hutch-med.com |
| Name | Affiliation | Role |
|---|---|---|
| Weili Zhao | Ruijin Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Not yet recruiting | Shanghai | Shanghai Municipality | China |
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| HMPL-760 Placebo |
| Drug |
Patients will receive HMPL-760 placebo once daily (QD) orally. |
|
| R-GemOx | Drug | 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. |
|
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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 |
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) | 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) | 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) | 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 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 |
| Up to approximately two years |
| PK characteristics of HMPL-760 in patients with R/R DLBCL when administered in combination with R-GemOx | 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)] |
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 | maximum concentration in steady-state (Cmax,ss) | Up to approximately two years |
| Pharmacokinetic parameters of gemcitabine and oxaliplatin when combined with HMPL-760 | 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 | 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 | 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 | The distribution volume calculated based on the terminal elimination phase (Vz/F )(if applicable) | Up to approximately two years |
| Baoding NO.1 Central Hospital | Not yet recruiting | Baoding | China |
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| Beijing GoBroad Hospital | Not yet recruiting | Beijing | China |
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| BEIJING TONGREN HOSPITAL, Capital Medical University | Not yet recruiting | Beijing | China |
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| The First Affiliated Hospital of Bengbu Medical College | Not yet recruiting | Bengbu | China |
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| The First Hospital of Jilin University | Not yet recruiting | Changchun | China |
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| Hunan Cancer Hospital | Not yet recruiting | Changsha | China |
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| People's Hospital of Hunan Province | Not yet recruiting | Changsha | China |
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| The Second Xiangya Hospital of Central South University | Not yet recruiting | Changsha | China |
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| Sichuan Provincial People's Hospital | Not yet recruiting | Chengdu | China |
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| West China Hospital of Sichuan University | Not yet recruiting | Chengdu | China |
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| Chongqing University Cancer Hospital | Not yet recruiting | Chongqing | China |
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| Quanzhou First Hospital.Fujian | Not yet recruiting | Fujian | China |
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| Fujian Medical University Union Hospital | Not yet recruiting | Fuzhou | China |
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| Sun Yat-sen University Cancer Center | Not yet recruiting | Guangzhou | China |
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| ZhuJiang Hospital of Southern Medical University（The Second Clinical Medical College） | Not yet recruiting | Guangzhou | China |
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| The Affiliated Hospital of Guizhou Medical University | Not yet recruiting | Guiyang | China |
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| The First Affiliated Hospital, Zhejiang University | Not yet recruiting | Hangzhou | China |
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| Zhejiang Cancer Hospital | Not yet recruiting | Hangzhou | China |
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| Harbin Medical University Cancer Hospital | Not yet recruiting | Harbin | China |
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| The Second Affiliated Hospital of Anhui Medical University | Not yet recruiting | Hefei | China |
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| Qilu Hospital of Shandong University | Not yet recruiting | Jinan | China |
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| Shandong Cancer Hospital & Institute | Not yet recruiting | Jinan | China |
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| Jiangxi Cancer Hospital | Not yet recruiting | Nanchang | China |
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| Jiangsu Cancer Hospital | Not yet recruiting | Nanjing | China |
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| The First Affiliated Hospital of Guangxi Medical University | Not yet recruiting | Nanning | China |
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| The Affiliated Hospital of Qingdao University | Not yet recruiting | Qingdao | China |
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| Ruijin Hospital, Shanghai Jiaotong University School of Medicine | Not yet recruiting | Shanghai | China |
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| Tongji Hospital of Tongji University | Not yet recruiting | Shanghai | China |
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| Shengjing Hospital of China Medical University | Not yet recruiting | Shenyang | China |
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| Shanxi Provincial Cancer Hospitial | Not yet recruiting | Taiyuan | China |
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| North China University of Science and Technology Affiliated Hospital | Not yet recruiting | Tangshan | China |
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| Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College | Recruiting | Tianjin | China |
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| Tianjin Medical University Cancer Institute & Hospital | Not yet recruiting | Tianjin | China |
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| Tianjin People's Hospital | Not yet recruiting | Tianjin | China |
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| Cancer Hospital Affiliated to Xinjiang Medical University | Not yet recruiting | Ürümqi | China |
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| Hubei Cancer Hospital | Not yet recruiting | Wuhan | China |
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| Wuhan Union Hospital of China | Not yet recruiting | Wuhan | China |
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| The First Affiliated Hospital of Xi'an Jiaotong University | Not yet recruiting | Xi'an | China |
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| Henan Cancer Hospital | Not yet recruiting | Zhengzhou | China |
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| The First Affiliated Hospital of Zhengzhou University | Not yet recruiting | Zhengzhou | China |
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| ID | Term |
|---|---|
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| ID | Term |
|---|---|
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D000069283 | Rituximab |
| D000093542 | Gemcitabine |
| D007267 | Injections |
| D000077150 | Oxaliplatin |
| ID | Term |
|---|---|
| D058846 | Antibodies, Monoclonal, Murine-Derived |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D006571 | Heterocyclic Compounds |
| D003841 | Deoxycytidine |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D004333 | Drug Administration Routes |
| D004358 | Drug Therapy |
| D013812 | Therapeutics |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |
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