DZD8586 combined with immunochemotherapy for diffuse large B‑cell lymphoma

A Phase Ib/II, Multicenter Study to Evaluate the Efficacy and Safety of DZD8586 Combination Therapy in Diffuse Large B-cell Lymphoma

This trial tests whether adding DZD8586 to standard immunochemotherapy helps people with diffuse large B‑cell lymphoma respond better and what side effects occur.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Dizal Pharmaceuticals (industry)
• Drugs / interventions: chemotherapy, Radiation
• Locations: 13 sites (Beijing and 12 other locations)
• Trial ID: NCT07059650 on ClinicalTrials.gov

What this trial studies

This phase 1/2 trial gives DZD8586 together with one of three immunochemotherapy regimens (R‑CHOP, R‑GemOx, or BR) to patients with diffuse large B‑cell lymphoma to measure safety, objective response rate, and drug levels. Cohort 1 enrolls previously untreated patients with stage II–IV disease, while cohorts 2 and 3 enroll patients who relapsed or are refractory after prior R‑CHOP–like therapy, including those unsuitable for or who refuse transplant. The study's primary outcomes include objective response rate and incidence and severity of adverse events, with pharmacokinetic sampling to measure DZD8586 levels when given with chemotherapy. The trial is being conducted at major hospitals in Beijing, Changsha, and Chengdu, China.

Who should consider this trial

Good fit: Ideal candidates are adults with pathologically confirmed DLBCL who are either newly diagnosed (stage II–IV) with life expectancy ≥12 months or relapsed/refractory after prior R‑CHOP–like therapy with life expectancy ≥6 months and who meet other protocol criteria.

Not a fit: Patients with other lymphoma subtypes, very poor performance status or short life expectancy, uncontrolled serious comorbidities, or who cannot travel to the China study sites are unlikely to benefit or be eligible for this trial.

Why it matters

Potential benefit: If successful, this combination could improve response rates and extend disease control for some people with DLBCL while defining safety and dosing.

How similar studies have performed: Combining targeted agents with immunochemotherapy has helped some DLBCL subgroups in prior studies, but DZD8586 itself is a novel agent with limited published clinical data, so this specific approach is relatively untested.

Eligibility criteria

Inclusion Criteria:

* Cohort 1:

  1. Patients with pathologically confirmed DLBCL who have not received prior anti-lymphoma therapy.
  2. Disease stage II to IV by Ann Arbor Classification.
  3. Life expectancy ≥ 12 months.
* Cohort 2, 3:

  1. Pathologically confirmed DLBCL patients who have received adequate first-line treatment containing CD20 monoclonal antibody and anthracyclines (such as R-CHOP-like regimen).
  2. Relapsed or refractory to first-line R-CHOP-like regimen.
  3. 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.
  4. Life expectancy ≥ 6 months.
* Patients must also meet all of the following criteria to be included in this study:

  1. All patients must provide a signed and dated written informed consent prior to any study-specific procedure, sampling, and analysis.
  2. Patients must be ≥ 18 years of age at the time of informed consent.
  3. ECOG status score of 0 to 2.
  4. 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.
  5. Adequate bone marrow hematopoietic reserve and organ function.
  6. No uncontrolled medical complications.
  7. Patients should be able to follow the relevant requirements of this study for medication and follow-up.
  8. Willing to comply with contraceptive restrictions.

Exclusion Criteria:

* 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:

  1. Indolent lymphoma-transformed DLBCL, primary mediastinal lymphoma, lymphoma involving the central nervous system, or DLBCL with MYC and BCL2 rearrangements.
  2. Prior use of BTK inhibitors.
  3. Vaccination with live attenuated vaccines or viral vector vaccines within 4 weeks prior to enrollment.
  4. 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.
  5. 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.
  6. Clinically significant cardiac disorders. History of thrombotic diseases, stroke or intracranial hemorrhage within 6 months.
  7. Active infectious diseases.
  8. 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.
  9. The patient has been diagnosed with other malignant diseases other than B-cell lymphoma within the past 2 years.
  10. Patients with hypersensitivity to DZD8586 drug excipients or other chemical analogues.
  11. Patients with severe or uncontrolled systemic diseases, including poorly controlled hypertension and active bleeding constitution.
  12. Serious medical or psychiatric illness that could affect participation in the study or could compromise the ability to consent
  13. Women who are pregnant or breastfeeding.

Where this trial is running

Beijing and 12 other locations

• 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)

Study contacts

• Principal investigator: Huang — Sun Yat-Sen University Cancer Center
• Study coordinator: Mengling Zhong

Conditions: Diffuse Large B-Cell Lymphoma