Mantle cell lymphoma (MCL) combines the highly progressive nature of aggressive lymphoma with the incurable nature of indolent lymphoma. Most patients are diagnosed at an advanced stage, often with involvement of lymph nodes, bone marrow, gastrointestinal tract, and extranodal organs. The successive availability of previous generations of BTK inhibitors has significantly improved patient prognosis, but drug resistance and relapse remain a major challenge to long-term survival.
On June 4, 2026, according to the latest information on the official website of the National Medical Products Administration (NMPA) of China, the Class 1 innovative drug lobrutinib tablets submitted by Guangzhou Lupeng Pharmaceutical Co., Ltd. was approved for marketing . The drug is indicated for adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have previously received at least two systemic therapies (including Bruton's tyrosine kinase [BTK] inhibitors) .

According to publicly available information, lobubrutinib is the world's first fourth-generation covalent and non-covalent BTK inhibitor , developed by Lupeng Pharmaceutical's proprietary BeyondX® oral drug chemistry platform. This drug has a dual mechanism of action: it covalently binds to wild-type BTK, while reversibly binding to C481 mutants (such as C481S/F/R), and irreversibly acts on gated mutations such as T474I.

Compared with previous drugs of the same type, lobubrutinib relies on a dual mechanism of "covalent + non-covalent" to effectively overcome multiple drug resistance mutations such as C481S, and has higher target selectivity, significantly reducing the risk of adverse reactions such as cardiovascular events and severe bleeding.

The NMPA's approval of lobrutinib for the treatment of relapsed or refractory mantle cell lymphoma is primarily based on positive results from a nationwide, multicenter, open-label, single-arm registration phase II clinical trial (ROCK-1 study) . Led by Professors Jun Zhu and Yuqin Song of Peking University Cancer Hospital, and with the participation of 41 centers across the country, this study aimed to evaluate the efficacy and safety of lobrutinib monotherapy in patients with relapsed or refractory MCL who had previously received covalently administered BTK inhibitors.
Data as of June 5, 2025, showed that lobrutinib monotherapy achieved an objective response rate (ORR ) of 63.9%, a complete response rate (CR) of 23%, and a median duration of response (mDOR) of 16.5 months in BTKi-reversed (post-BTKi) R/R MCL patients. All patients enrolled in this study had undergone multiple lines of therapy and had previously received covalent BTK inhibitor therapy; more than one-third of them had received two or more BTK inhibitors. The baseline characteristics of the patients suggested that the overall patient population was treatment-resistant and had a poor prognosis.

In terms of safety, no cardiac events such as atrial fibrillation/atrial flutter of any grade occurred during the study, and no cases of drug discontinuation due to adverse reactions occurred. The incidence of other adverse reactions was relatively low and generally controllable.

In May 2024 , lobutinib was included in the list of breakthrough therapies by the CDE for the indication of adult relapsed or refractory non-germinal center B-cell diffuse large B-cell lymphoma (R/R non-GCB DLBCL) who had received at least two lines of prior therapy. The corresponding pivotal registration phase II clinical trial ( ROCK-2 ) was launched at the end of 2025 .
Furthermore, results from a Phase I study conducted in the United States showed that lobrutinib achieved an ORR of 78.3% in BTK inhibitor-prevented chronic lymphocytic leukemia ( CLL ) , with an estimated median progression-free survival ( mPFS ) of 28.1 months . In January 2026 , a global Phase III head-to-head clinical trial (ROCKET-CLL study, NCT07342478) comparing lobrutinib with the third-generation non-covalent BTK inhibitor pitutinib for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) was officially launched , marking a new phase in the global development of lobrutinib.

In August 2024, Hansoh Pharmaceutical and Lupeng Pharmaceutical entered into a strategic collaboration on lobrutinib. Hansoh Pharmaceutical acquired the rights to research, registration, manufacturing, and commercialization of the product in China (including Hong Kong, Macau, and Taiwan) for all non-oncology indications. Hansoh Pharmaceutical will pay Lupeng Pharmaceutical an upfront payment and potential payments for research, registration, and sales-based commercialization milestones totaling no more than RMB 729 million, as well as tiered royalties based on the highest double digits of future net sales of the product.

It is worth mentioning that in April 2026 , lobrutinib was included for the first time in the "Chinese Society of Clinical Oncology ( CSCO ) Lymphoma Diagnosis and Treatment Guidelines ( 2026 Edition) ," and was listed as a Level II recommendation in the treatment of relapsed / refractory mantle cell lymphoma ( R/R MCL ) . As a fourth-generation BTK inhibitor with both covalent and non-covalent mechanisms of action, the launch of lobrutinib will provide a groundbreaking new treatment option for many mantle cell lymphoma patients facing treatment difficulties after failing previous-generation BTK inhibitor therapy.

https://mp.weixin.qq.com/s/FIUhZuSW7wVzlb_dITbDmA