Safety and Efficacy of Rocbrutinib in Patients with Relapsed/Refractory Marginal Zone Lymphoma

Song, Yuqin

Oral and Poster Abstracts
623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster I

Research, Clinical trials, Lymphomas, Clinical Research, Diseases, Indolent lymphoma, Lymphoid Malignancies

Yuqin Song, MD¹, Qingqing Cai, PhD², Keshu Zhou, MD³^*, Ming Jiang⁴^*, Zhengming Jin, M.D.⁵^*, Lei Zhang, PhD, MD⁶^*, Xiuhua Sun⁷^*, Haiyan Yang⁸^*, Lanfang Li⁹^*, Kaiyang Ding¹⁰^*, Junyuan Qi, MD¹¹^*, Hongmei Jing¹²^*, Wei Yang¹³^*, Min Zhou¹⁴^*, Jun Ma¹⁵^*, Zhigang Peng¹⁶^*, Wei Xu¹⁷^*, Hui Zhou, MD¹⁸, Li Yu¹⁹^*, Yuankai Shi, MD²⁰^*, Guohui Cui²¹^*, Zheng Wang²²^*, Nawei Liu²²^*, Yejiang Lou, PhD²³^*, Yue Shen, PhD²²^*, Yi Chen, PhD²⁴^*, Fenlai Tan²²^* and Jun Zhu, MD²⁵^*

¹Department of Lymphoma, Peking University Cancer Hospital, BEIJING, China
²Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
³Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
⁴Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan, China
⁵Department of Hematology, Collaborative Innovation Center of Hematology, Institute of Blood and Marrow Transplantation, the First Affiliated Hospital of Soochow University, Suzhou, China
⁶The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
⁷The Second Hospital of Dalian Medical University, Dalian, China
⁸Zhejiang Cancer Hospital, Hangzhou, China
⁹Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
¹⁰Department of Hematology, The First Affiliated Hospital of University of Science and Technology of China, Anhui, China
¹¹State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
¹²Department of Hematology, Peking University Third Hospital, Beijing, China
¹³Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China
¹⁴Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
¹⁵Harbin Institute of Hematology & Oncology, Harbin, China
¹⁶The First Affiliated Hospital of Guangxi Medical University, Nanning, China
¹⁷Lymphoma Center, Department of Hematology, Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
¹⁸Department of Lymphoma & Hematology, Hunan Cancer Hospital and Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
¹⁹The Second Affiliated Hospital of Nanchang University, Nanchang, China
²⁰Cancer Hospital (Institute), CAMS & PUMC, Beijing, China
²¹Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
²²Guangzhou Lupeng Pharmaceutical Co., Ltd., Guangzhou, China
²³Guangzhou Lupeng Pharmaceutical Co., Ltd., Hangzhou, China
²⁴Newave Pharmaceutical Inc., Pleasanton, CA
²⁵Department of Lymphoma, Key Laboratory of Carcinogenesis and Translational Research (Minis-try of Education), Peking University Cancer Hospital & Institute, Beijing, China

Background: Marginal zone lymphoma (MZL) comprises approximately 8% to 12% of non-Hodgkin lymphomas (NHL), characterized by malignant cells that consistently rely on B-cell receptor signaling. Covalent Bruton’s tyrosine kinase inhibitors (cBTKis) have shown activity in relapsed or refractory (R/R) MZL, achieving an overall response rate (ORR) of 40-60%. Rocbrutinib, a new-generation BTKi, is highly selective with excellent bioavailability and a unique dual binding mechanism: covalent binding, otherwise non-covalent with C481 mutation. Here, we present the efficacy and safety outcomes of rocbrutinib in patients with R/R MZL enrolled in an ongoing phase 1 study (NCT04993690) in B-cell malignancies.

Methods: Patients with R/R MZL who received ≥1 line of prior therapies, including an anti-CD20 antibody-containing regimen, were enrolled. Adverse events (AEs) were graded per CTCAE v5.0 and disease responses were assessed per Lugano 2014 response criteria.

Results: Between 30 July 2021 and 31 May 2024, 30 R/R MZL patients were enrolled and received treatment of rocbrutinib at 100mg (n=3), 150mg (n=21) and 200mg (n=6) QD respectively, till disease progression or unacceptable toxicities. The median age was 65 (range, 32 to 79) years. 22 were with extra-nodal MZL (73.3%), and 5 nodal MZL (16.7%). Most patients (90%) were with advanced-stage disease; 46.7% had intermediate to high-risk disease per International Prognostic Index (IPI). All 30 patients received at least one prior line of CD20-based treatment per study eligibility. The median line of prior therapies was 1 (range, 1-4), and 26.7% of patients had refractory disease at study entry.

The most common treatment emergent adverse events (TEAEs) (occurring in ≥20% patients) were platelet count decreased or thrombocytopenia (30.0%), white blood cell count decreased (26.7%), serum creatinine increased (23.3%), petechiae (23.3%), infectious pneumonia (23.3%), neutrophil count decreased or neutropenia (20.0%) and hyperuricemia (20.0%), most of which were Grade 1. 13 (43.3%) patients experienced ≥grade 3 TEAE. Serious AEs occurred in 9 (30.0%) patients. Dose interruptions and dose reductions due to AEs were observed in 8 patients (26.7%) and 1 patient (3.3%), respectively; however, no AE led to drug discontinuation. One fatal case of hypotension was assessed by the investigator as unlikely related to the study treatment.

Of 29 efficacy evaluable patients with median follow-up of 10.9 months (range: 2.0-32.0), 21 (72.4%) achieved response including 3 (10.3%) complete response (CR). The ORR for the extra-nodal (n=21), nodal (n=5), and unknown (n=3) subtypes was 76.2%, 80.0%, and 33.3%, respectively. For the 13 patients who had received ≥2 lines of prior therapies, the ORR was 53.8% with a CR rate of 15.4%. Among the 7 patients who had refractory disease, the ORR was 71.4%. Of 2 patients who had progressed on prior cBTKi, 1 (50.0%) responded to rocbrutinib. As of data cutoff, the median duration of response (DOR) and median progression-free survival (PFS) have not reached.

Conclusion: Rocbrutinib is well tolerated and has shown promising anti-tumor activity in terms of response rate in patients with R/R MZL. Longer follow-up is needed to assess the long-term benefit.

Disclosures: Chen: Newave Pharmaceutical Inc.: Current Employment, Current holder of stock options in a privately-held company, Honoraria, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties: Newave Pharmaceutical Inc.

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1635 Safety and Efficacy of Rocbrutinib in Patients with Relapsed/Refractory Marginal Zone Lymphoma