Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Conditions
Keywords
HMPL-760, R-GemOx (rituximab, gemcitabine, and oxaliplatin), R/R DLBCL
Brief summary
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.
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.
Interventions
DRUGHMPL-760
Patients will receive HMPL-760 once daily (QD) orally.
DRUGHMPL-760 Placebo
Patients will receive HMPL-760 placebo once daily (QD) orally.
DRUGR-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.
Sponsors
Hutchmed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free survival (PFS) | 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. |
| End of treatment (EOT) | 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). |
| Systemic antitumor therapy | 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). |
| Overall survival (OS) | Up to approximately two years | OS is defined as the time from randomization to death due to any cause. |
| systematic anti-tumor therapy | 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). |
| Premature withdrawal from study treatment | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Independent review committee (IRC)-assessed PFS | Up to approximately two years | Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014). |
| IRC- and investigator-assessed objective response rate (ORR) | 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) |
| IRC- and investigator-assessed complete response rate (CRR) | Up to approximately two years | Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR) |
| IRC- and investigator-assessed duration of response (DoR) | 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 |
| IRC- and investigator-assessed clinical benefit rate (CBR) | Up to approximately two years | Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD) |
| IRC- and investigator-assessed time to response (TTR) | 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) |
| Safety Endpoints | 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. |
| PK characteristics of HMPL-760 in patients with R/R DLBCL when administered in combination with R-GemOx | 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. |
Countries
China
Contacts
CONTACTDongmei Chen, CPL
PRINCIPAL_INVESTIGATORWeili Zhao
Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Outcome results
None listed