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3119 Rocbrutinib, a New-Generation BTK Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Non-GCB Diffuse Large B Cell Lymphoma

Program: Oral and Poster Abstracts
Session: 627. Aggressive Lymphomas: Pharmacologic Therapies: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical trials, Lymphomas, Clinical Research, Diseases, Aggressive lymphoma, Lymphoid Malignancies
Sunday, December 8, 2024, 6:00 PM-8:00 PM

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: Approximately 40% of patients with diffuse large B-cell lymphoma (DLBCL) either fail to respond to initial standard therapy or experience a relapse, resulting in a dismal prognosis. Non-germinal center B-cell-like (GCB) DLBCL has an even worse outcome. The early data of covalent bruton’s tyrosine kinase inhibitor (cBTKi) in R/R non-GCB DLBCL showed an overall response rate (ORR)of 20-40%. Rocbrutinib (LP-168) is a highly selective, new-generation BTKi with superb bioavailability and unique dual binding mode: covalent binding, otherwise non-covalent with C481 mutation. Here, we report the safety and efficacy of Rocbrutinib monotherapy in the R/R non-GCB DLBCL from an ongoing phase 1 study (NCT04993690) in B-cell malignancies.

Methods: Patients(age>=18 years with R/R DLBCL after ≥2 prior lines of therapies including ≥1 anti-CD20 antibody-containing regimen were enrolled. Adverse events (AEs) were graded per CTCAE v5.0 and responses of patients with R/R non-GCB DLBCL were assessed according to the Lugano 2014 response criteria.

Results: Between 30 July 2021 and 31 May 2024, 33 efficacy evaluable patients with R/R non-GCB DLBCL were enrolled. They received daily treatment of rocbrutinib at 100mg (n=2), 150mg (n=23), 200mg (n=6) and 300mg (n=2) respectively till progressive disease or unacceptable toxicities. The median age was 59 (range, 21-73) years old; 20 (60.6%) were male. One-third of the patients had at least one lesion of >=5cm in diameter. 51.5% had intermediate to high-risk disease per International Prognostic Index (IPI). The median line of prior therapies was 2 (range, 2-5) and most patients (87.9%) were refractory to any prior treatments.

The most common treatment emergent adverse events (TEAEs) (occurring in ≥20% patients) were neutrophil count decreased or neutropenia (63.6%), white blood cell count decreased (45.5%), platelet count decreased or thrombocytopenia (45.5%), anemia (30.3%), petechiae (30.3%), lymphocyte count increased (27.3%), lymphocyte count decreased (27.3%), hypertriglyceridemia (24.2%), hyperuricemia (24.2%) and serum creatinine increased (21.2%), most of which were grade 1. 14 (42.4%) patients experienced ≥grade 3 TEAEs . Serious AEs (lung infection, grade 3) occurred in 2 (6.1%) patients. 8 patients (24.2%) had dose interruptions due to AEs, but no AE has led to dose adjustment or drug discontinuation. AE leading to death was reported for one patient (lung infection, not related to rocbrutinib).

Of 33 efficacy evaluable patients with median follow-up of 6.7 months (range: 1.8-26.9), 20 (60.6%) achieved response including 11 (33.3%) complete response (CR). For the 10 patients who had received ≥3 lines of therapy previously, the ORR and CR rate was 90% and 50%, respectively. Notably, the response rate of rocbrutinib in patients refractory to last prior therapy (n=28) was 57.1%, with CR rate of 28.6%. As of data cut-off, duration of response (DOR), progression-free survival (PFS), and overall survival (OS) are not mature yet.

Conclusion: In conclusion, rocbrutinib has demonstrated a high CR and response rate in heavily pre-treated R/R non-GCB DLBCL with favorable safety profiles. Based on the encouraging data, rocbrutinib has received breakthrough therapy designation for the treatment of patients with non-GCB DLBCL who have received at least 2 lines of prior therapies from China CDE (center of drug evaluation). A Phase 1b study of rocbrtuinib in combination with R-CHOP for untreated non-GCB DLBCL is also ongoing (NCT06251180).

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.

*signifies non-member of ASH