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)
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- Hutchmed
- Enrollment
- 240
- Locations
- 50
- Primary Endpoint
- Progression-free survival (PFS)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Sign the ICF and be able to follow the requirements of study protocol;
- •Age ≥18 years;
- •ECOG performance status score between 0 and 2;
- •Histopathologically confirmed diagnosis of DLBCL;
- •The investigator judges that the patient's current condition requires further treatment;
- •Patients should have at least one bi-dimensionally measurable lesion;
- •Expected survival is more than 12 weeks;
Exclusion Criteria
- •Patients with known primary or secondary central nervous system lymphoma (CNSL) or the presence of clinical symptoms suggestive of CNSL;
- •Women who are pregnant (positive pregnancy test during the screening period) or breastfeeding;
- •Organ insufficiency;
- •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);
- •History of significant organ bleeding, including gastrointestinal bleeding, hematencephalon, haemoptysis, etc., within 8 weeks prior to the first dose of study drug;
- •Known risk of bleeding, such as coagulation factor deficiency, vascular hemophilia; or the patient is receiving vitamin K antagonist (warfarin);
- •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);
- •Clinically significant active infection;
Arms & Interventions
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.
Intervention: R-GemOx (Drug)
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.
Intervention: HMPL-760 Placebo (Drug)
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.
Intervention: HMPL-760 (Drug)
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.
Intervention: R-GemOx (Drug)
Outcomes
Primary Outcomes
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.
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).
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).
Overall survival (OS)
Time Frame: Up to approximately two years
OS is defined as the time from randomization to death due to any cause.
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).
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).
Secondary Outcomes
- IRC- and investigator-assessed clinical benefit rate (CBR)(Up to approximately two years)
- IRC- and investigator-assessed time to response (TTR)(Up to approximately two years)
- Independent review committee (IRC)-assessed PFS(Up to approximately two years)
- IRC- and investigator-assessed objective response rate (ORR)(Up to approximately two years)
- IRC- and investigator-assessed complete response rate (CRR)(Up to approximately two years)
- IRC- and investigator-assessed duration of response (DoR)(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(At the end of Cycle 4 (each cycle is 21 days)])