Rocbrutinib Plus R-CHOP Elicits Responses in Previously Untreated B-Cell Lymphomas

Rocbrutinib combined with rituximab (Rituxan), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) generated responses in all efficacy-evaluable patients with previously untreated non–germinal center B-cell (non-GCB) lymphomas diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), according to first results from a phase 1b study (NCT06251180) presented at the 2026 ESMO Congress.¹

Among efficacy-evaluable patients with non-GCB DLBCL or MCL (n = 17), the overall response rate (ORR) was 100%, including a complete response (CR) rate of 76.5% and a partial response (PR) rate of 23.5%. Among patients who received at least 4 cycles of the combination (n = 15), the ORR was 100%, the CR rate was 86.7%, and the PR rate was 13.3%. No patients in either group experience stable disease or progressive disease.

Of the patients with a CR who underwent circulating tumor DNA (ctDNA)–based minimal residual disease (MRD) testing (n = 8), 87.5% were MRD negative.

Responses occurred early, with a median time to response of 1.25 months (range, 1.15-2.63) and a median time to CR of 2.69 months (range, 1.41-8.21). At a median follow-up of 5.46 months (range, 0.07-17.58) among patients with DLBCL, no disease progression or deaths had occurred, and the median progression-free survival (PFS) was not reached. Additionally, the ORR was 100% at each dose level, and CR rates were 100% at dose level 1 (n = 2), 60.0% at dose level 2 (n = 5), and 80.0% at dose level 3 (n = 10).

"If we can deepen this initial response by targeting a pathway the lymphoma depends on, we may be able to reduce the risk of relapse. That is the rationale for starting the combination up front," lead study author Qingqing Cai, MD, PhD, of Sun Yat-sen University Cancer Center in Guangzhou, China, explained in an exclusive interview with OncLive®.

How was the phase 1b trial of rocbrutinib plus R-CHOP in B-cell lymphoma designed?

The open-label, multicenter trial included patients who were were 18 to 70 years of agewith previously untreated DLBCL, MCL, or marginal zone lymphoma (MZL). Patients also needed to have an ECOG performance status of 2 or less, measurable disease per Lugano criteria, adequate organ function and no central nervous system involvement.

If patients had primary central nervous system lymphoma, primary mediastinal large B-cell lymphoma, a history of indolent lymphoma, known bleeding diseases, or received prior solid organ transplantation or hematopoietic stem cell transplantation, they were not included in the trial.²

Patients received rocbrutinib at 100 mg (dose level 1), 150 mg (dose level 2), or 200 mg (dose level 3) once daily with R-CHOP for the first 6 21-day cycles, followed by rituximab for cycles 7 and 8, in 21-day cycles. Patients with a CR or a PR, for those with MCL or MZL, continued rocbrutinib maintenance for up to 24 cycles.

Primary end points were safety, recommended phase 3 dose, and pharmacokinetics. Secondary end points included ORR, CR rate, duration of response, PFS, event-free survival, and overall survival.

Among all enrolled patients (n = 22), the median age was 58.5 years (range, 38-69), and 54.5% of patients were male. Most patients had an ECOG performance status of 1 (86.4%), and the rest had a performance status of 0 (13.6%). Overall, 90.9% of patients had non-GCB DLBCL and 9.1% had MCL. Regarding disease stage, 27.3% of patients had stage II disease, 18.2% had stage III disease, and 54.5% had stage IV disease; no patients had stage I disease.

Among patients with DLBCL (n = 20), International Prognostic Index scores were 0 to 1 in 25.0%, 2 in 45%, 3 in 25%, and 4 to 5 in 5%, and 35% had double-expressor lymphoma. Additionally, 13.6% of all patients had bulky disease and 50.0% had 2 or more extranodal sites involved.

What was the safety profile of rocbrutinib plus R-CHOP in previously untreated B-cell lymphoma?

All patients experienced treatment-emergent adverse effects (TEAEs), all of which included grade 3 or higher TEAEs, and 45.5% experienced serious TEAEs. TEAEs led to rocbrutinib dose interruptions in 72.7% of patients, dose reductions in 9.1%, and treatment discontinuation in 4.5%. Notably, the one patient who discontinued treatment, did so due to lung cancer that developed during maintenance. TEAEs led to dose reductions of any R-CHOP component in 68.2% of patients, but no patient permanently discontinued R-CHOP because of AEs. No TEAEs led to death across all patients in the trial.

No dose-limiting toxicities were observed, and the most common treatment-related AEs (TRAEs) were hematologic, particularly neutropenia (any grade, 86.4%; grade 3 or higher, 72.7%), which occurred predominantly during the combination period and was managed with dose modifications and granulocyte colony-stimulating factor support. Pneumonia was the most common grade 3 or higher nonhematologic TRAE (18.2%).

“As of [the] data cutoff, we saw no dose-limiting toxicity, atrial fibrillation or flutter, major bleeding, or treatment-related deaths. Cytopenias and infections still require close management. A large study with longer follow-up is needed to understand uncommon [risks],” Cai explained.

What are the next steps for rocbrutinib in non-GCB DLBCL?

“For this combination, I would want longer follow-up and a randomized trial that can test durable benefit and safety against [the] frontline standard. It’s [a] possibility because [a] pivotal randomized phase 2 trial [NCT07189065] in relapsed or refractory non-GCB DLBCL comparing [rocbrutinib] monotherapy with investigator’s choice of [bendamustine plus rituximab] or [lenalidomide plus rituximab] is ongoing in China, but it is too early to predict approval in DLBCL or whether [rocbrutinib] will be first,” Cai emphasized. “I’m encouraged by the activity, [but] the clinical evidence and regulatory review [will determine] whether it becomes a treatment option.”

References

1. Cai Q, Xia Y, Hong H, et al. First report of a phase Ib study of rocbrutinib, a fourth-generation Bruton's tyrosine kinase inhibitor, in combination with R-CHOP in previously untreated B-cell lymphoma. Presented at: 2026 ESMO Congress; October 23-27, 2026; Madrid, Spain. Abstract 1457O.
2. Phase Ib study of rocbrutinib in combination with R-CHOP in patients with newly diagnosed B-cell non-Hodgkin lymphoma. ClincialTrials.gov. Updated September 11, 2026. Accessed November 3, 2026.