Lupeng Pharmaceutical's Fourth-Generation BTK Inhibitor Rocbrutinib Approved in China for R/R MCL, Global Phase 3 ROCKET-CLL Trial Underway
核心洞察
China's NMPA granted accelerated approval to rocbrutinib, a fourth-generation dual covalent and non-covalent BTK (搜索) inhibitor, for relapsed/refractory mantle cell lymphoma patients who have received at least two prior systemic therapies including BTK inhibitors.
Rocbrutinib is engineered to overcome multiple resistance mutations including C481X, T474X, and L528W, positioning it as a potential best-in-class therapy in the post-BTKi setting.
The global Phase 3 ROCKET-CLL trial has enrolled its first patient, evaluating rocbrutinib head-to-head against pirtobrutinib in R/R CLL/SLL patients who progressed after prior covalent BTK (搜索) inhibitor therapy.
GUANGZHOU, China — Lupeng Pharmaceutical (搜索) today announced that the National Medical Products Administration (NMPA) has granted accelerated approval to rocbrutinib (development code: LP-168) for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (搜索) (R/R MCL) who have received at least two prior systemic therapies, including BTK (搜索) inhibitors. The approval marks a significant milestone for the fourth-generation BTK inhibitor, which features a unique dual covalent and non-covalent mechanism designed to address resistance that has limited earlier-generation therapies.
Dr. Tan Fenlai, co-founder and CEO of Lupeng Pharmaceutical (搜索), described the approval as "a major milestone in Lupeng Pharmaceutical's development," adding that it "will bring a new and effective treatment option to MCL patients who have experienced disease progression after earlier-generation BTK (搜索) inhibitor therapy."
A Differentiated Mechanism of Action
Rocbrutinib, independently developed by Lupeng Pharmaceutical (搜索), is the world's first fourth-generation BTK (搜索) inhibitor combining both covalent (irreversible) and non-covalent (reversible) binding capabilities. This dual mechanism enables inhibition of both wild-type and C481-mutant BTK while overcoming multiple resistance mutations, including C481X, T474X, and L528W. The drug was developed on Lupeng's proprietary BeyondX Oral MedChem Platform, which the company describes as capable of efficiently developing next-generation, globally best-in-class small molecule targeted drugs featuring novel mechanisms of action.
Dr. Chen Yi, co-founder and CSO of the company, stated that "the market launch of rocbrutinib is a successful example of Lupeng's 'innovation methodology,' proving that the company's unique 'Beyond the Rule of 5,' BeyondX Oral MedChem Platform, can efficiently develop next-generation, globally best-in-class small molecule targeted drugs."
Global Phase 3 ROCKET-CLL Trial Launches
Beyond the MCL approval in China, rocbrutinib is advancing in a global registrational program. Lupeng Pharmaceutical (搜索), through its wholly-owned subsidiaries Newave Pharmaceutical Inc. and Guangzhou Lupeng Pharmaceutical Co., Ltd., announced the enrollment of the first patient in the global Phase 3 ROCKET-CLL trial (NCT07342478).
The first study site was activated on April 28, 2026, at OptumCare Cancer Care Center in Las Vegas, Nevada, under the leadership of Dr. Russell Gollard. On May 20, 2026, Dr. Gollard and his team enrolled the first patient, marking a key milestone in the global development of rocbrutinib.
ROCKET-CLL is a randomized, open-label, multicenter Phase 3 study expected to enroll approximately 306 adult patients worldwide. The study is co-led by Dr. Jennifer Woyach at Ohio State University and Dr. John Byrd at the University of Pittsburgh Medical Center, with participation by leading academic centers in the US, EU, China, and Australia.
Participants are randomized 1:1 to receive once-daily oral rocbrutinib (200 mg) or pirtobrutinib (200 mg). The primary endpoint is progression-free survival (PFS), with secondary endpoints including overall survival (OS, key secondary endpoint), overall response rate (ORR), duration of response (DOR), time to next treatment (TTNT), event-free survival (EFS), and safety and tolerability. Exploratory endpoints include patient-reported outcomes, health-related quality of life, and biomarker analyses to further characterize treatment response and resistance mechanisms. Enrollment is expected to be completed by early Q4 2027, with an interim analysis planned for 2029.
Clinical Evidence Supporting Rocbrutinib
Dr. Jennifer Woyach highlighted the clinical data underpinning the development program: "Based on clinical findings from the US Phase 1 study, among CLL patients previously treated with cBTKi and/or ncBTKi, patients treated at dose levels of 200 mg/day or higher, the overall response rate was 78.3%, with an estimated median progression-free survival of 28.1 months for doses of at least 100 mg/daily."
These results, presented at ASH 2025, underscore the potential of rocbrutinib's differentiated mechanism in addressing the significant unmet need among patients who have progressed on prior BTK (搜索) inhibitor therapy.
Expanding Indications
Lupeng Pharmaceutical (搜索) is continuing to advance clinical studies of rocbrutinib in other indications. The company has received Breakthrough Therapy Designation (BTD) in China for adult patients with relapsed or refractory non-germinal center B-cell-like diffuse large B-cell lymphoma (搜索) (R/R non-GCB DLBCL) who have received at least two prior lines of therapy, making it the first BTK (搜索) inhibitor in China — and the only one globally — to receive such designation in this indication.
Dr. Tan Fenlai affirmed the company's commitment: "Going forward, we will continue to advance clinical studies of rocbrutinib in other indications such as diffuse large B-cell lymphoma (搜索) (DLBCL) and chronic lymphocytic leukemia/small lymphocytic lymphoma (搜索) (CLL/SLL), to help more patients with various hematologic malignancies."