This study will treat patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). It will assess the anti-tumor efficacy and safety of birelentinib plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) vs placebo plus R-CHOP.

Inclusion Criteria:

• Age 18-70 years
• ECOG score 0-2
• Pathologically confirmed DLBCL unspecified (DLBCL, NOS)
• No prior anti-lymphoma therapy
• Ann Arbor Stages II - IV
• IPI score ≥ 3, or IPI score 1 - 2 and LDH > 1.3 × ULN and/or lesion diameter ≥ 7 cm
• Adequate bone marrow and organ function
• Willing to comply with contraceptive restrictions

Exclusion Criteria:

• Indolent lymphoma or Richter transformation, primary mediastinal lymphoma, lymphoma invading the central nervous system or high-grade lymphoma with MYC and BCL2 rearrangements.
• Vaccination with live attenuated vaccines or viral vector vaccines within 4 weeks prior to treatment.
• 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, anti-tumor traditional Chinese medicine.
• Major surgery within 4 weeks or anticipated surgery after the start of this study.
• Clinically significant cardiac disorders. History of thrombotic diseases, stroke or intracranial hemorrhage within 6 months.
• Active infectious diseases.
• Peripheral neuropathy ≥ Grade 2 (as defined by CTCAE version 6.0)
• 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.
• Diagnosed with other malignant diseases other than B-cell lymphoma within the past 2 years.
• Patients with severe or uncontrolled systemic diseases, including poorly controlled hypertension and active bleeding constitution.
• Patients with a history of hypersensitivity to any component of the R-CHOP regimen, DZD8586 drug excipients, or other chemical analogues.
• Serious medical or psychiatric illness that could affect participation in the study or could compromise the ability to consent.
• Women who are pregnant or breastfeeding.