A Phase III Study of HMPL-760 in Combination With R-GemOx Versus Placebo in Combination With R-GemOx in Relapsed/Refractory DLBCL

Phase 3Not Yet RecruitingNCT07409428

Hutchmed240 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

240

Conditions

Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Interventions

HMPL-760DRUG

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

HMPL-760 PlaceboDRUG

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

R-GemOxDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 exclusion criteria); 8. Clinically significant active infection;

Outcomes

Primary Outcomes

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.

Time frame: 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).

Time frame: 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).

Time frame: Up to approximately two years

Overall survival (OS)

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

Time frame: 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).

Time frame: Up to approximately two years

Premature withdrawal from study treatment

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).

Central Contacts

Dongmei Chen, CPL

CONTACT

86-21-20671794 dongmeic@hutch-med.com

Data from ClinicalTrials.gov

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Secondary Outcomes

Independent review committee (IRC)-assessed PFS

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

Time frame: Up to approximately two years

IRC- and investigator-assessed objective response rate (ORR)

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

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)

Time frame: 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

Time frame: 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)

Time frame: 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)

Time frame: Up to approximately two years

Safety Endpoints

* 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: 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.

Time frame: At the end of Cycle 4 (each cycle is 21 days)]