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

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 · Drug: R-GemOx

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: HMPL-760 Placebo · Drug: R-GemOx

Patients will receive HMPL-760 once daily (QD) orally.

Patients will receive HMPL-760 placebo once daily (QD) orally.

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.

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.

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).

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).

Time frame: Up to approximately two years

OS is defined as the time from randomization to death due to any cause.

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).

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).

Time frame: Up to approximately two years

Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014).

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)

Time frame: Up to approximately two years

Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR)

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

Time frame: Up to approximately two years

Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD)

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)

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.

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.

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.

Time frame: Up to approximately two years

Human metabolites of HMPL-760 when co-administered with R-GemOx

Time frame: Up to approximately two years

maximum concentration in steady-state (Cmax,ss)

Time frame: Up to approximately two years

time to maximum concentration in steady-state (Tmax,ss)

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)

Time frame: Up to approximately two years

The rate at which the drug is eliminated from the body (CL/F) (if applicable )

Time frame: Up to approximately two years

The distribution volume calculated based on the terminal elimination phase (Vz/F )(if applicable)

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)