844TiP - Orelabrutinib combined with rituximab for the treatment of elderly patients with newly diagnosed non-GCB diffuse large B-cell lymphoma (DLBCL) under the guidance of genetic subtype: A prospective, multicenter, single-arm, response-adaptive clinical study (Origin)

Background

DLBCL is a highly heterogeneous disease with generally poorer prognosis in elderly patients. To optimize therapeutic outcomes, it is imperative to delve into the specific genetic subsets and target BTKi toward precise patient populations based on their signatures. R-CHOP combined with BTKi showed that the complete response rate (CRR) of MCD subtype increased from 54% to 85% in phase II Guidance-01. Orelabrutinib (O) was designed to have fewer off-target activities and improved efficacy and safety, exhibiting a synergistic effect with rituximab (R). This study aimed to evaluate the efficacy and safety of O plus R followed by O plus miniCHOP in treatment-naïve elderly patients with non-GCB DLBCL under the guidance of genotyping.

Trial design

This multicenter, single-arm study (ChiCTR2300077256) will enroll 63 patients (age ≥65 years) with histopathologically confirmed naïve, CD20-positive, non-GCB DLBCL, and ≥1 measurable lesion from 7 sites in China. Patients will receive one cycle of induction therapy with O (150 mg, day 1-21) plus R (375 mg/m², day 1). Based on the response to OR regimen and tumor genotype, responders (≥25% reduction in lesions) or non-responders with MCD, BN2, and N1 subtypes will receive O (150 mg/day) plus miniCHOP (cyclophosphamide 400 mg/m², day 2; vincristine 1.4mg/m², day 2; etoposide 35 mg/m² or liposomal etoposide 15-17.5 mg/m², day 2; and prednisone 45 mg/m², day 2-6) for 6 cycles every 3 weeks until disease progression or unacceptable toxicity. Primary endpoint is CRR after 6 cycles of O+miniCHOP; second endpoints are 2-year event-free survival/progression-free survival, CRR by subtypes in responders or non-responders, objective response rate, and safety.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.