Dr Cai on the Rationale for Evaluating Rocbrutinib Plus R-CHOP in Non-GCB DLBCL and MCL

“The unique dual-binding property, selectivity, favorable [pharmacokinetic/pharmacodynamic] profile, and early monotherapy clinical activity [of rocbrutinib] gave us a reason to evaluate this strategy.”

Qingqing Cai, MD, PhD, deputy director of the Department of Medical Oncology, a professor, and a chief physician at Sun Yat-sen University Cancer Center, discussed the rationale behind a phase 1b trial (NCT06251180) evaluating the BTK inhibitor rocbrutinib (LP-168) plus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated B-cell lymphoma, with a focus on non–germinal center B-cell (non-GCB) diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL). Cai also noted factors that distinguish the agent from other BTK inhibitors.

First results from the study were presented at the 2026 ESMO Congress. Among efficacy-evaluable patients with non-GCB DLBCL or MCL (n = 17), the overall response rate was 100%, including a complete response rate of 76.5%. No dose-limiting toxicities, atrial fibrillation or flutter, major bleeding events, or treatment-related deaths were reported.

Rocbrutinib is an oral BTK inhibitor distinguished by its dual-binding mechanism, Cai explained. In preclinical studies, the agent bound covalently to wild-type BTK and noncovalently to C481-mutated BTK, Cai said. Rocbrutinib is also highly selective for BTK, which provides a rationale for limiting off-target effects, she added.

These features, together with the encouraging monotherapy efficacy observed in an early-phase studies of rocbrutinib in patients with non-GCB DLBCL who had received at least 2 prior lines of therapy, made the agent a candidate worth exploring in treatment-naive DLBCL, Cai noted.

Cai acknowledged that prior experience with BTK inhibitor–based combinations is important context. In the phase 3 PHOENIX trial (NCT01855750), ibrutinib (Imbruvica) plus R-CHOP did not meet the study’s primary end point, and toxicity compromised chemotherapy delivery in older patients, Cai said. Other similar studies include the phase 3 ESCALADE trial (NCT04529772) of acalabrutinib (Calquence) plus R-CHOP, as well as the BELIEVE-01 trial (NCT05234684) of orelabrutinib plus R-CHOP, which focused on the MCD genetic subtype of DLBCL, Cai explained.