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

NCT07122609 | Not Yet Recruiting Phase 2

• 1 other identifier: pirto-R-Gemox
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• complete response rate(CRR)

  CRR after treated by pirto-R-GemOx±pola

  Up to 6 cycles (each cycle is 21 days)

Secondary Outcomes (4)

• Objective response rate(ORR)

  Up to 6 cycles (each cycle is 21 days) ± pola

• Progression-free survival (PFS)

  Up to 6 cycles (each cycle is 21 days)

• Overall Survival (OS)

  up to 6 cycles(each cycle is 21 days)

• undetectable MRD rate

  Up to 6 cycles (each cycle is 21 days) ± pola

Study Arms (1)

pirtobrutinib+R-GemOx with or without polatuzumab vedotin

EXPERIMENTAL

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.

Drug: Pirtobrutinib; Drug: R-GemOx; Drug: Polatuzumab Vedotin

Interventions

Pirtobrutinib DRUG

Dose:200mg，d1-21

Also known as: LOXO-305

pirtobrutinib+R-GemOx with or without polatuzumab vedotin

R-GemOx DRUG

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

pirtobrutinib+R-GemOx with or without polatuzumab vedotin

Polatuzumab Vedotin DRUG

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

pirtobrutinib+R-GemOx with or without polatuzumab vedotin

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200025, China

Location

MeSH Terms

Conditions

Recurrence

Interventions

pirtobrutinib; polatuzumab vedotin

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Weili Zhao, Professor

  Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Weili Zhao, Professor

CONTACT

86 02164370045; zwl_trial@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: First Deputy Director of Shanghai Institute of Hematology

Study Record Dates

• First Submitted: July 27, 2025
• First Posted: August 14, 2025
• Study Start: August 5, 2025
• Primary Completion (Estimated): August 15, 2026
• Study Completion (Estimated): August 15, 2027
• Last Updated: August 14, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)