Polatuzumab plus R‑CHP with a genotype‑guided targeted drug for untreated DLBCL

A Study to Evaluate the Efficacy and Safety of Genotype-guided Targeted Agents in Combination With POLA-RCHP VERSUS POLA-RCHP in Patients With Previously Untreated Diffuse Large B-cell Lymphoma

This test will see if adding a genotype‑guided targeted drug to polatuzumab plus R‑CHP helps adults in China with untreated diffuse large B‑cell lymphoma who show limited early ctDNA response.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 152 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Ruijin Hospital (Academic / other)
• Drugs / interventions: Zanubrutinib, polatuzumab, rituximab, cyclophosphamide, doxorubicin, prednisone
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06803693 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 trial compares polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola‑RCHP) versus the same backbone plus a genotype‑guided targeted agent (Pola‑RCHP‑X) in Chinese patients with previously untreated CD20‑positive DLBCL. Eligible patients are 18–75 years old with IPI 2–5, ECOG 0–2, adequate organ function, and are selected after showing less than a 3.0 log‑fold decrease in circulating tumor DNA (ctDNA) following one cycle of Pola‑R‑CHP. The trial uses early ctDNA decline as a biomarker to enrich for patients who may benefit from adding a targeted agent. Outcomes include comparative measures of efficacy and safety between the two treatment arms.

Who should consider this trial

Good fit: Ideal candidates are Chinese adults aged 18–75 with previously untreated CD20‑positive DLBCL, IPI 2–5, ECOG 0–2, adequate hematologic and cardiac function, and a ctDNA drop of less than 3.0 LFC after one cycle of Pola‑R‑CHP.

Not a fit: Patients with a strong early ctDNA decline, significant cardiac dysfunction, uncontrolled cytopenias, prior lymphoma therapy, or those unable to attend the Shanghai site are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, this approach could improve remission rates by personalizing frontline therapy for patients who show poor early ctDNA response.

How similar studies have performed: Polatuzumab added to immunochemotherapy has shown benefit in prior trials (for example POLARIX), but adding genotype‑guided targeted agents based on early ctDNA response in the frontline setting is a relatively novel strategy with limited prior evidence.

Eligibility criteria

Inclusion Criteria:

* Signed Informed Consent Form
* Age 18-75 years at the time of signing Informed Consent Form and willingness to comply with study protocol procedures
* Previously untreated participants with CD20-positive DLBCL
* IPI score 2-5
* ECOG Performance Status of 0, 1, or 2
* After 1 cycle of Pola-R-CHP, ctDNA decreased by \< 3.0 LFC
* Life expectancy ≥ 6 months
* Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
* Adequate hematologic function (unless due to underlying disease, as established for example, by extensive bone marrow involvement or due to hypersplenism secondary to involvement of the spleen by DLBCL per the investigator for which blood product transfusions are permitted) defined as follows:

  * Hemoglobin ≥ 9.0 g/dL without packed RBC transfusion during 7 days before first treatment
  * ANC ≥ 1.0 x 10\^9/L
  * PLT ≥ 75 x 10\^9/L

Exclusion Criteria:

* Contraindication to any of the individual components of Pola-RCHP or Zanubrutinib/Lenalidomide/ Decitabine
* Prior solid organ transplantation or SCT
* Current diagnosis of the following: Follicular lymphoma grade 3B; mediastinal grey zone lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt lymphoma; PCNSL
* Significant or extensive history of cardiovascular disease such as New York Heart Association Class III or IV cardiac disease or Objective Assessment Class C or D, myocardial infarction within the last 6 months prior to the start of Cycle 1, unstable arrhythmias, or unstable angina
* History or presence of an abnormal ECG that is clinically significant in the investigator's opinion
* Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma):

  * Serum AST and ALT ≥ 2.5 x ULN
  * Total bilirubin ≥ 1.5 x ULN
  * Serum creatinine clearance \< 30 mL/min (using Cockcroft-Gault formula)
* Any active infection within 7 days prior to Cycle 1 Day 1 that would impact participant safety
* Positive test results for chronic hepatitis B infection (defined as positive hepatitis B surface antigen \[HBsAg\] serology)：Participants with occult or prior hepatitis B infection (defined as positive total hepatitis B core antibody and negative HbsAg) may be included if hepatitis B virus (HBV) DNA is undetectable at the time of screening. Such participants must be willing to undergo HBV DNA testing every month and appropriate antiviral therapy as indicated
* Positive test results for hepatitis C (hepatitis C virus \[HCV\] antibody serology testing)：Participants positive for HCV antibody are eligible only if PCR is negative for HCV RNA
* Participants with a history of progressive multifocal leukoencephalopathy
* Pregnancy or breastfeeding, or intention of becoming pregnant during the study or within 12 months after final dose of Pola-RCHP-X
* Other concurrent and uncontrolled medical conditions that, in the opinion of the investigator, would affect the patient's participation in the study

Where this trial is running

Shanghai, Shanghai Municipality

• Ruijin Hospital, Shanghai JiaoTong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Weili Zhao

Conditions Diffuse Large B-Cell Lymphoma