Study of HMPL-760 Plus R-GemOx Versus Placebo Plus R-GemOx in Relapsed/Refractory DLBCL

Phase 2

Recruiting

• Conditions: Relapsed/Refractory Diffuse Large B-Cell Lymphoma
• Interventions: Drug: HMPL-760 planned dose 1; Drug: R-GemOx; Drug: HMPL-760 placebo planned dose 1; Drug: HMPL-760 planned dose 2; Drug: HMPL-760 placebo planned dose 2

• Registration Number: NCT06601504
• Lead Sponsor: Hutchmed

Brief Summary

The goal of this study is to evaluate the efficacy 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 (R/R DLBCL).

Detailed Description

A Phase II Randomized, 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 (R/R DLBCL). The study phases include screening period, treatment period, safety observation period, PFS follow-up period, and OS follow-up period.

Study Timeline

• Study First Submitted: 2024-09-08
• Study First Submitted QC: 2024-09-14
• Study First Posted: 2024-09-19
• Status Verified: 2024-11
• Study Start: 2024-11-05
• Last Update Submitted: 2024-11-19
• Last Update Posted: 2024-11-21
• Primary Completion: 2026-05-12
• Study Completion: 2026-11-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Sign the Informed consent form(ICF) and be able to follow the requirements of study protocol;
2. Age ≥18 years;
3. Eastern Cooperative Oncology Group (ECOG) performance status 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. Toxicities from prior anticancer therapy not resolved to Grade ≤ 1 (except for alopecia and decreased appetite);
8. Clinically significant active infection;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen	HMPL-760 planned dose 1	Group A: Patients will receive HMPL-760 planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m\^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m\^2 ivgtt is given, followed by oxaliplatin 100 mg/m\^2 ivgtt on day 2 of each cycle.
Group A: HMPL-760 planned dose 1 once daily (QD) in combination with R-GemOx regimen	R-GemOx	Group A: Patients will receive HMPL-760 planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m\^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m\^2 ivgtt is given, followed by oxaliplatin 100 mg/m\^2 ivgtt on day 2 of each cycle.
Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen	R-GemOx	Patients will receive HMPL-760 placebo planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m\^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m\^2 ivgtt is given, followed by oxaliplatin 100 mg/m\^2 ivgtt on day 2 of each cycle.
Group B: HMPL-760 placebo planned dose 1 once daily (QD) in combination with R-GemOx regimen	HMPL-760 placebo planned dose 1	Patients will receive HMPL-760 placebo planned dose 1 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m\^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m\^2 ivgtt is given, followed by oxaliplatin 100 mg/m\^2 ivgtt on day 2 of each cycle.
Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen	R-GemOx	Patients will receive HMPL-760 planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m\^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m\^2 ivgtt is given, followed by oxaliplatin 100 mg/m\^2 ivgtt on day 2 of each cycle.
Group C: HMPL-760 planned dose 2 once daily (QD) in combination with R-GemOx regimen	HMPL-760 planned dose 2	Patients will receive HMPL-760 planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m\^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m\^2 ivgtt is given, followed by oxaliplatin 100 mg/m\^2 ivgtt on day 2 of each cycle.
Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen	R-GemOx	Patients will receive HMPL-760 placebo planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m\^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m\^2 ivgtt is given, followed by oxaliplatin 100 mg/m\^2 ivgtt on day 2 of each cycle.
Group D: HMPL-760 placebo planned dose 2 once daily (QD) in combination with R-GemOx regimen	HMPL-760 placebo planned dose 2	Patients will receive HMPL-760 placebo planned dose 2 once daily (QD) orally from Cycle 1 Day 1 until disease progression(PD), patient death, intolerable toxicity, etc., in combination with R-GemOx regimen in 21-day cycle for a total of 6 cycles. Rituximab 375 mg/m\^2 ivgtt is given on day 1 of each cycle, and gemcitabine 1000 mg/m\^2 ivgtt is given, followed by oxaliplatin 100 mg/m\^2 ivgtt on day 2 of each cycle.

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Up to approximately 2 years	Progression-free survival (PFS): Efficacy is evaluated using the Lugano Efficacy Evaluation Criteria for Malignant Lymphoma (Cheson 2014).

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 2 years	Objective Response Rate (ORR) is defined as the ratio of patients who reached complete response (CR) or partial response (PR), as assessed by investigator.
Complete response (CR) rate	Up to approximately 2 years	Complete response (CR) rate is defined as the ratio of patients with who reached complete response (CR), as assessed by investigator.
Duration of response (DoR)	Up to approximately 2 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, as assessed by investigator.
Clinical benefit rate (CBR)	Up to approximately 2 years	Defined as the ratio of patients with complete response (CR), partial response (PR), or stable disease (SD).
Time to response (TTR)	Up to approximately 2 years	Time To Response (TTR) is defined as the time from the start of treatment to the first objective response rate (ORR), as assessed by investigator.
Overall survival (OS)	Up to approximately 2 years	Overall Survival (OS) is defined as the time from randomization to death due to any cause.
Safety Endpoints of adverse events	Up to approximately 2 years	Incidence and severity of treatment-emergent adverse events (TEAEs), incidence of serious adverse events (SAEs), 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 5.0 (NCI CTCAE 5.0).
Pharmacokinetic(PK) profile of HMPL-760 in combination with R-GemOx	At the end of Cycle 7 (each cycle is 21 days)	Apparent volume of distribution at steady-state (Vz,ss/F) of drug (if applicable)

Trial Locations

Locations (23)

Anhui Provincial Cancer Hospital; 🇨🇳 Hefei, Anhui, China

China-Japan Friendship Hospital; 🇨🇳 Beijing, Beijing, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China

The Third Affiliated Hospital,SUNYAT-SEN UNIVERSITY; 🇨🇳 Guangzhou, Guangdong, China

The Second People's Hospital of Shenzhen; 🇨🇳 Shenzhen, Guangdong, China

Guangxi Medical University Cancer Hospital; 🇨🇳 Nanning, Guangxi, China

Affiliated Hospital od Chengde Medical University; 🇨🇳 Chengde, Hebei, China

Wuhan Union Hospital of China; 🇨🇳 Wuhan, Hebei, China

Harbin First Hospital; 🇨🇳 Harbin, Heilongjiang, China

Harbin Medical University Cancer Hospital; 🇨🇳 Harbin, Heilongjiang, China

Henan Cancer Hospital; 🇨🇳 Zhengzhou, Henan, China

The First Affiliated Hospital of Zhengzhou University; 🇨🇳 Zhengzhou, Henan, China

Hunan Cancer Hospital; 🇨🇳 Changsha, Hunan, China

Jiangsu Province Hospital; 🇨🇳 Nanjing, Jiangsu, China

Jiangxi Cancer Hospital; 🇨🇳 Nanchang, Jiangxi, China

The First Affiliated Hospital of Nanchang University; 🇨🇳 Nanchang, Jiangxi, China

Shengjing Hospital of China Medical University; 🇨🇳 Shenyang, Liaoning, China

Shandong Cancer Hospital & Institute; 🇨🇳 Jinan, Shandong, China

West China Hospital of Sichuan University; 🇨🇳 Chengdu, Sichuan, China

Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College; 🇨🇳 Tianjin, Tianjin, China

The First Affiliated Hospital, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China

Ruijin Hospital, Shanghai Jiaotong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China