ROCK-2: An ongoing open-label, randomized, multicenter phase 2 study of rocbrutinib versus investigator's choice of therapy in patients with R/R non-GCB DLBCL.

Abstract

TPS7106 Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Aberrant activation of the Bruton's tyrosine kinase (BTK)-related signaling pathway is present in the non-GCB subtype of DLBCL (Davis et al. Nature 2010). Multiple BTK inhibitors (BTKi) have demonstrated efficacy in relapsed or refractory (R/R) non-GCB DLBCL (Strati et al. Haematologica. 2021; Wilson et al. Nat Med. 2015; Yang et al. Blood Adv. 2022), however, there remains room for further improvement. Rocbrutinib is a novel, highly selective, the fourth generation covalent (irreversible) and non-covalent (reversible) BTKi. Phase 1 study showed that in 45 patients with R/R non-GCB DLBCL who had received ≥2 prior lines of systemic therapy, rocbrutinib monotherapy achieved an overall response rate (ORR) of 57.8% and a complete response (CR) rate of 31.3%( Song et al. CSCO. 2025). This article describes the design and progress of a phase 2 pivotal study aimed at comparing the efficacy and safety of rocbrutinib versus investigator's choice of therapy in patients with R/R non-GCB DLBCL. Methods: ROCK-2 (NCT07189065; CTR20253693) is an open-label, randomized, multicenter phase 2 study conducted in China. Eligible patients must have non-GCB DLBCL, not otherwise specified (NOS) per the 2017 WHO classification, received ≥2 prior lines of systemic therapy. Additionally, patients must have measurable disease, an ECOG performance status of 0-2, and adequate hematologic and organ function. Key exclusion criteria include central nervous system involvement, DLBCL transformed from indolent lymphoma, prior refractoriness to BTK-targeting agents, uncontrolled systemic diseases, active infection. Approximately 150 eligible subjects will be randomized 1:1 to receive either rocbrutinib or BR/R 2 , stratified by the number of prior lines of therapy (2 vs ≥3) and International Prognostic Index (IPI) score (0-2 vs 3-5). Subjects in the experimental group will receive rocbrutinib [200 mg once daily (QD)] until disease progression or unacceptable toxicity. Subjects in the control group will receive either BR or R 2 according to the investigator's choice. The BR regimen consists 6 cycles of rituximab (375 mg/m² on day 1) plus bendamustine (90 mg/m²/d on days 1-2). The R 2 regimen consists of rituximab (375 mg/m² on day 1 of cycles 1-6) plus lenalidomide (20 mg QD on days 1-21 of each 28d-cycle until disease progression or unacceptable toxicity). The primary endpoint is ORR assessed by Independent Review Committee (IRC) according to the 2014 Lugano criteria. Secondary endpoints include ORR assessed by investigator (INV), and CR rate, progression-free survival (PFS), duration of response (DOR), time to response (TTR), overall survival (OS) assessed by IRC or INV. The first subject was enrolled on Nov 27 th ,2025. Recruitment is ongoing. Clinical trial information: NCT07189065 .