Pirtobrutinib in Combination With Rituximab, Gemcitabine, Oxaliplatin With or Without Polatuzumab Vedotin in Covalent BTK Inhibitor-Pretreated Relapsed/Refractory Diffuse Large B-Cell Lymphoma

NCT ID: NCT07122609

Last Updated: 2025-08-14

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-05
• Study Completion Date: 2027-08-15

Brief Summary

This is a prospective, single arm trial in patients with ≥ 18 years with relapsed and refractory DLBCL. Aim of this study is to evaluate the efficacy and safety of pirtobrutinib in combination with rituximab, gemcitabine, and oxaliplatin with or without polatuzumab vedotin (Pirto-R-GemOx±pola) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) previously treated with covalent BTK inhibitors.

Conditions

Relapsed and Refractory DLBCL

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

pirtobrutinib+R-GemOx with or without polatuzumab vedotin

DLBCL patients will receive Pirto-R-GemOx for a total of 6 treatment cycles (21days per cycle). Patient who is CD79b positive and has not previously received polatuzumab Vedotin will combine with polatuzumab Vedotin.The efficacy will be evaluated every 3 cycles, young patients with CR will receive ASCT, CR patients who do not undergo ASCT or PR patients will continued for 3 cycles.If the efficacy is evaluated as CR or PR after 6 cycles, then ASCT for young patients, and lenalidomide maintenance treatment for elderly patients for 2 years (25mg, day 1-21, Q4W). ctDNA testing will be performed at baseline、before the second course、and at the end of treatment.

Group Type: EXPERIMENTAL

Pirtobrutinib

Intervention Type: DRUG

Dose:200mg，d1-21

R-GemOx

Intervention Type: DRUG

Dose: Rituximab: 375mg/m2, d1; Gemcitabine: 1000mg/m2, d2; Oxaliplatin:100mg/m2, d2

Polatuzumab Vedotin

Intervention Type: DRUG

Dose: 1.8mg/kg，iv，d1 (For patient who is CD79b positive and has not previously received polatuzumab Vedotin)

Interventions

Pirtobrutinib

Dose:200mg，d1-21

Intervention Type: DRUG

R-GemOx

Dose: Rituximab: 375mg/m2, d1; Gemcitabine: 1000mg/m2, d2; Oxaliplatin:100mg/m2, d2

Intervention Type: DRUG

Polatuzumab Vedotin

Dose: 1.8mg/kg，iv，d1 (For patient who is CD79b positive and has not previously received polatuzumab Vedotin)

Intervention Type: DRUG

Other Intervention Names

LOXO-305

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed DLBCL (2016 WHO criteria) of MCD, BN2, N1 subtypes, double-expressor, intravascular large B-cell lymphoma, or other BTK-sensitive subtypes
• Disease progression/relapse after covalent BTK inhibitor therapy
• ≥1 measurable lesion (nodal >15mm/extranodal >10mm) on PET/CT within 28 days
• Eastern Cooperative Oncology Group (ECOG) 0-2
• age ≥18 years
• Adequate organ function:

ANC ≥0.5×10⁹/L ；Platelets ≥50×10⁹/L (transfusion-independent)；Bilirubin ≤1.5×ULN; ALT/AST ≤2.5×ULN；Cr ≤1.5×ULN or CrCl ≥30mL/min；LVEF ≥50% (NYHA class <III)

• Life expectancy >3 months
• Sign the written ICF, and be able to comply with the visits and related procedures stipulated in the protocol;
• Female subjects of childbearing potential or male subjects with female partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last treatment.

Exclusion Criteria

• DLBCL with central nervous system (CNS) or meningeal involvement
• Histologically transformed DLBCL
• Contraindications or hypersensitivity to any drug in the combination regimen
• Major surgery within 4 weeks prior to treatment (excluding vascular access placement or biopsy)
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's judgment, may compromise patient safety or compliance with study procedures
• Poorly controlled cardiac clinical symptoms or diseases, including:

i. NYHA Class II or higher heart failure ii. Unstable angina iii. Myocardial infarction within 1 year iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment/intervention

• Active hemorrhage
• Poorly controlled systemic bacterial, viral, fungal, or parasitic infections (excluding fungal nail infections), or other clinically significant active diseases that render patients unsuitable for trial participation per investigator assessment
• Patients with:Active chronic hepatitis B or C.Positive HBsAg and/or HBcAb or HCV antibodies at screening must demonstrate HBV DNA ≤2,500 copies/mL (or 500 IU/mL) to exclude active HBV/HCV infection requiring treatment.HBsAg/HBcAb-positive patients must receive antiviral prophylaxis.

HIV-infected patients and/or AIDS patients

• Inability to swallow tablets, malabsorption syndrome, or any gastrointestinal disorder/ dysfunction that may impair drug absorption
• Lactating or pregnant women
• Psychiatric disorders or inability to provide informed consent
• Any other condition deemed unsuitable for study participation by the investigator

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ruijin Hospital

OTHER

Sponsor Role: lead

Responsible Party

Zhao Weili

First Deputy Director of Shanghai Institute of Hematology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Weili Zhao, Professor

Role: PRINCIPAL_INVESTIGATOR

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Locations

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Weili Zhao, Professor

Role: CONTACT

zwl_trial@163.com

86 02164370045

Facility Contacts

Weili Zhao, Professor

Role: primary

zhaoweili_sih@163.com

021-64370045

Other Identifiers

pirto-R-Gemox

Identifier Type: -

Identifier Source: org_study_id