Efficacy and safety of rocbrutinib, a highly selective 4th-generation Bruton's tyrosine kinase inhibitor, in relapsed/refractory Mantle Cell Lymphoma (R/R MCL): Updated results from the phase 1 study

Abstract Background The advent of novel targeted and immunotherapeutic approaches, particularly Bruton's tyrosine kinase inhibitors (BTKis), have significantly improved survival outcomes in patients with mantle cell lymphoma (MCL), with acceptable safety profiles. However, therapeutic challenges (e.g. acquired resistance, intolerance, etc.) remain. Rocbrutinib is a highly selective, 4th-generation BTKi that integrates the advantages of covalent irreversible inhibition and non-covalent binding, and demonstrates superior pharmacokinetic profiles in humans. Previously, data have demonstrated that rocbrutinib induces high response rate and durable responses in heavily pre-treated patients with R/R MCL, particularly those with prior BTKi exposure (Yuqin Song et al. 2023 ASH). Here, we present updated data from the ongoing phase I trial LP-168-CN101 (NCT04993690) evaluating rocbrutinib in patients with BTKi naïve R/R MCL. Methods Patients aged 18–80 with R/R MCL who had received ≥1 line of therapies (including ≥1 line anti-CD20 antibody-based regimens) were treated with rocbrutinib monotherapy until disease progression. Adverse events (AEs) were graded per CTCAE v5.0, and efficacy was assessed per Lugano 2014 criteria. Results As of June 15, 2025, 28 BTKi-naïve R/R MCL patients were enrolled and received rocbrutinib 100 mg (n=4), 150 mg (n=23), or 200 mg (n=1) once daily (QD) treatment. The median age was 61 years (range: 40–77). Blastoid/pleomorphic variants accounted for 17.9% of cases, and 45.7% of patients were with intermediate- or high-risk per MCL international prognostic index (MIPI). The median number of prior lines of therapies was 1 (range: 1-3), with 14.3% of patients having undergone autologous stem cell transplantation. The most common treatment-related AEs (TRAEs, incidence≥20%) (any grade;≥grade 3) included decreased neutrophil count (46.4%; 7.1%), decreased platelet count (39.3%; 3.1%), increased blood creatinine (35.7%; 0), decreased white blood cell count (32.1%; 0), petechiae (32.1%; 0), anemia (28.6%; 0), and decreased lymphocyte count (21.4%; 0), most of which were grade 1. No atrial fibrillation,≥grade 3 hypertension or hemorrhage occurred. Dose interruption due to TRAEs occurred in 6 (21.4%) patients, but only 1 patient underwent dose reduction. No drug discontinuation or death due to TRAEs has occurred. Of 28 efficacy evaluable patients, the overall response rate (ORR) was 89.3%, with a complete response (CR) rate of 57.1%. After median follow-up of 21.2 (range: 0.9-43.1) months, PFS is not matured yet. The 18-month PFS rate was 74.3%. Conclusion Consistent with previously reported data in patients with post BTKi R/R MCL, rocbrutinib demonstrates a favorable safety profile and robust efficacy in patients with BTKi naïve R/R MCL, with high response rates, deep remissions, and durable responses.