DZD8586 Combination Therapy in Patients With Diffuse Large B-cell Lymphoma (TAI-SHAN12)

NCT07059650 | Recruiting Phase 1

• 1 other identifier: DZ2024B0001
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 13

Brief Summary

This study will treat patients with diffuse large B-cell lymphoma (DLBCL). It will assess the anti-tumor efficacy and safety of DZD8586 combination therapy by using objective response rate and the incidence and severity of adverse events. It will also measure the levels of DZD8586 in the body when combined with immunochemotherapy regimens.

Conditions

Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Part A: Incidence and severity of adverse events

  Approximately 5 years

• Part B: Objective response rate (ORR)

  Approximately 5 years

Secondary Outcomes (20)

• Part A: Objective response rate (ORR)

  Approximately 5 years

• Part A: Complete response rate (CRR)

  Approximately 5 years

• Part A: Time to response (TTR)

  Approximately 5 years

• Part A: Duration of Response (DoR)

  Approximately 5 years

• Part A: Progression-Free Survival (PFS)

  Approximately 5 years

Study Arms (1)

DZD8586 combination therapy

EXPERIMENTAL

3 cohorts are included in this arm: Cohort 1: Treatment naïve DLBCL patients will receive DZD8586 at the protocol defined dose level, combined with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens for 6 cycles, and then DZD8586 as maintenance therapy for patients who achieved (complete response) CR or (partial response) PR after 6 cycles combination therapy. Cohort 2: Relapsed/refractory DLBCL patients will receive DZD8586 at the protocol defined dose level, combined with R-GemOx (rituximab, gemcitabine, and oxaliplatin) regimens for 8 cycles, and then DZD8586 as maintenance therapy for patients who achieved CR or PR after 8 cycles combination therapy. Cohort 3: Relapsed/refractory DLBCL patients will receive DZD8586 at the protocol defined dose level, combined with BR (bendamustine and rituximab) regimens for 6 cycles, and then DZD8586 as maintenance therapy for patients who achieved CR or PR after 6 cycles combination therapy.

Drug: DZD8586+R-CHOP; Drug: DZD8586+R-GemOx; Drug: DZD8586+BR

Interventions

DZD8586+R-CHOP DRUG

DZD8586 at the protocol defined dose level (50 mg or 75 mg, po, qd) with R-CHOP (Rituximab: 375 mg/m2, IV, d1; Cyclophosphamide: 750 mg/m2, IV, d1; Doxorubicin: 50 mg/m2, IV, d1; Vincristine: 1.4 mg/m2, IV, d1; Prednisone: 100 mg, po, d1-5) in a 21-day cycle for 6 cycles. DZD8586 (pre-defined dose level, po, qd) as maintenance therapy for CR/PR patients.

DZD8586 combination therapy

DZD8586+R-GemOx DRUG

DZD8586 at the protocol defined dose level (50 mg or 75 mg, po, qd) with R-GemOx (Rituximab: 375 mg/m2, IV, d1; Gemcitabine: 1000 mg/m2, IV, d1; Oxaliplatin: 100 mg/m2, IV, d1) in a 21-day cycle for 8 cycles. DZD8586 (pre-defined dose level, po, qd) as maintenance therapy for CR/PR patients.

DZD8586 combination therapy

DZD8586+BR DRUG

DZD8586 at the protocol defined dose level (50 mg or 75 mg, po, qd) with BR (Bendamustine: 90 mg/m2, IV, d1-d2; Rituximab: 375 mg/m2, IV, d1) in a 21-day cycle for 6 cycles. DZD8586 (pre-defined dose level, po, qd) as maintenance therapy for CR/PR patients.

DZD8586 combination therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1:
• Patients with pathologically confirmed DLBCL who have not received prior anti-lymphoma therapy.
• Disease stage II to IV by Ann Arbor Classification.
• Life expectancy ≥ 12 months.
• Cohort 2, 3:
• Pathologically confirmed DLBCL patients who have received adequate first-line treatment containing CD20 monoclonal antibody and anthracyclines (such as R-CHOP-like regimen).
• Relapsed or refractory to first-line R-CHOP-like regimen.
• For patients who have received only one line of therapy, if the patient has not received autologous stem cell transplantation, the investigator needs to assess as unsuitable or the patient refuses intensive chemotherapy and hematopoietic stem cell transplantation.
• Life expectancy ≥ 6 months.
• Patients must also meet all of the following criteria to be included in this study:
• All patients must provide a signed and dated written informed consent prior to any study-specific procedure, sampling, and analysis.
• Patients must be ≥ 18 years of age at the time of informed consent.
• ECOG status score of 0 to 2.
• Presence of at least one radiologically measurable lesion in 2 perpendicular directions as assessed by CT or MRI and a positive lesion on PET/CT scan consistent with a tumor site identified by CT or MRI.
• Adequate bone marrow hematopoietic reserve and organ function.

You may not qualify if:

• Cohort 2, 3:
• a. Hematopoietic stem cell transplantation, cell therapy, or gene therapy within 90 days prior to first dose. Radiation therapy within 14 days prior to first dose. Chemotherapy and small-molecule targeted therapy were not terminated within 5 half-lives before the first dose; macromolecule drug therapy (such as antibody therapy) was not terminated within 28 days before the first dose.
• All patients should not be included in this study if they have any of the following conditions:
• Indolent lymphoma-transformed DLBCL, primary mediastinal lymphoma, lymphoma involving the central nervous system, or DLBCL with MYC and BCL2 rearrangements.
• Prior use of BTK inhibitors.
• Vaccination with live attenuated vaccines or viral vector vaccines within 4 weeks prior to enrollment.
• Currently taking vitamin K antagonists, taking 2 or more antiplatelet/anticoagulant drugs at the same time, drugs/herbs or supplements known to potently induce or inhibit CYP3A enzyme activity, proton pump inhibitor drugs, anti-tumor traditional Chinese medicine or failing to meet the protocol-specified withdrawal time before administration in this study.
• Major surgery within 4 weeks or anticipated surgery after the start of this study. Or insufficiently recovered from any toxicity and/or complications of previous intervention.
• Clinically significant cardiac disorders. History of thrombotic diseases, stroke or intracranial hemorrhage within 6 months.
• Active infectious diseases.
• Intractable nausea and vomiting that cannot be well controlled by supportive treatment, chronic gastrointestinal diseases, dysphagia, or previous surgical resection of the intestinal segment may affect the adequate absorption of the drug.
• The patient has been diagnosed with other malignant diseases other than B-cell lymphoma within the past 2 years.
• Patients with hypersensitivity to DZD8586 drug excipients or other chemical analogues.
• Patients with severe or uncontrolled systemic diseases, including poorly controlled hypertension and active bleeding constitution.
• Serious medical or psychiatric illness that could affect participation in the study or could compromise the ability to consent

Sponsors & Collaborators

• Dizal Pharmaceuticals: lead

Study Sites (13)

Peking University Third Hospital

Beijing, China

RECRUITING

Hunan Cancer Hospital

Changsha, China

NOT YET RECRUITING

West China Hospital of Sichuan University

Chengdu, China

RECRUITING

Guangdong Provincial People's Hospital

Guangzhou, China

RECRUITING

Sun Yat-sen University Cancer Center

Guangzhou, China

RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, China

RECRUITING

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, China

RECRUITING

Anhui Provincial Cancer Hospital

Hefei, China

RECRUITING

Linyi Cancer Hospital

Linyi, China

RECRUITING

Shanxi Cancer Hospital

Taiyuan, China

RECRUITING

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, China

RECRUITING

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Huang

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mengling Zhong

CONTACT

+86-21-61095852; mengling.zhong@dizalpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: July 11, 2025
• Study Start: August 19, 2025
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2030
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (13)