Head-to-head study highlights the distinctive features of lobrutenib as the world’s first covalent and non-covalent fourth-generation BTK inhibitor in overcoming resistance mutations
This head-to-head study aims to evaluate the efficacy and safety of the novel oral fourth-generation BTK inhibitor lobrutenib (LP-168) compared to pirtobrutinib in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) who have previously received covalent BTK inhibitor (cBTKi) therapy. Existing BTK inhibitors face challenges of drug resistance, necessitating the urgent development of next-generation therapies capable of overcoming resistance.
The first study site was officially launched on April 28, 2026, at the OptumCare Cancer Care Center in Las Vegas, Nevada, USA, led by principal investigator Dr. Russell Gollard, with the first patient enrolled on May 20, 2026. This marks a key milestone in advancing new treatment options for patients who have progressed after prior covalent BTK inhibitor therapy and face significant unmet clinical needs.
ROCKET-CLL is a randomized, open-label, multicenter Phase III clinical study expected to enroll 306 adult patients globally. The study is co-led by Dr. Jennifer Woyach of The Ohio State University and Dr. John Byrd of the University of Pittsburgh Medical Center, with participation from leading academic centers in the United States, the European Union, China, Australia, and other regions.
Subjects are randomized in a 1:1 ratio to receive either lobrutenib 200 mg or pirtobrutinib 200 mg once daily. The primary endpoint is progression-free survival (PFS), with secondary endpoints including overall survival (OS, a key secondary endpoint), overall response rate (ORR), duration of response (DOR), time to next treatment (TTNT), event-free survival (EFS), safety, and tolerability. Exploratory objectives include assessing patient-reported outcomes and health-related quality of life, as well as biomarker analyses aimed at exploring disease response and resistance mechanisms.
Subject enrollment for this study is expected to be completed by the end of 2027, with an interim analysis planned for 2029.
“The initiation of the ROCKET-CLL clinical trial represents a significant step in validating the differentiated covalent and non-covalent dual mechanism of action of lobrutenib,” said Dr. Jennifer Woyach of The Ohio State University. “Based on clinical data from the U.S. Phase I study, among CLL patients previously treated with covalent BTK inhibitors (cBTKi) and/or non-covalent BTK inhibitors (ncBTKi), those receiving 200 mg/day or higher doses achieved an overall response rate of 78.3%, and in the cohort receiving at least 100 mg/day, the estimated median progression-free survival was 28.1 months.”[1]
About Lobrutenib (LP-168)
Lobrutenib (LP-168), developed by Lupeng Pharmaceuticals’ proprietary BeyondX oral drug chemistry platform, is a novel oral, highly selective fourth-generation covalent and non-covalent BTK inhibitor. It not only covalently inhibits wild-type BTK but also non-covalently inhibits C481-mutated BTK, overcoming multiple resistance mutations caused by first-, second-, and third-generation BTK inhibitors, such as C481X, T474X, and L528W. This differentiated mechanism of action positions lobrutenib as a potential best-in-class BTK inhibitor following treatment failure or resistance to earlier-generation BTK inhibitors, demonstrating favorable safety and durable clinical efficacy in various B-cell malignancies.
A New Drug Application (NDA) for lobrutenib in relapsed or refractory mantle cell lymphoma (R/R MCL) has been accepted in China and is undergoing priority review by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). Additionally, lobrutenib has been granted Breakthrough Therapy Designation (BTD) in China for the indication of relapsed or refractory non-germinal center B-cell-like diffuse large B-cell lymphoma (R/R non-GCB DLBCL) in adult patients who have received at least two prior lines of therapy, making it the first in China and the only BTK inhibitor globally to receive such designation for this indication.
About Lupeng Pharmaceuticals
Lupeng Pharmaceuticals is a global, clinical-stage innovative biopharmaceutical company focused on developing next-generation therapies for hematologic malignancies and autoimmune diseases. Leveraging its proprietary BeyondX drug chemistry platform, the company has built a diversified pipeline centered on clinically validated targets such as BTK, Bcl-2, and Bcl-xL. Lupeng Pharmaceuticals is dedicated to drug innovation and actively advancing global expansion, striving to address unmet clinical needs worldwide with breakthrough therapies. For more information, please visit the official website: www.lupengbio.com
Forward-Looking Statements
This press release contains forward-looking statements, including those related to clinical development timelines, regulatory progress, and the potential therapeutic benefits of lobrutenib. These statements are subject to risks and uncertainties that could cause actual results to differ materially from expectations.
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