An open label, single arm, multicenter phase II study of the efficacy and safety of LP-168 monotherapy for relapsed or refractory mantle cell lymphoma.

TPS7098 Background: Targeting Bruton’s tyrosine kinase (BTK) has demonstrated impressive efficacy in relapsed or refractory mantle cell lymphoma (R/R MCL). Covalent BTK inhibitors (cBTKi) have produced extended disease remission and durable responses in R/R MCL. However, patients with continuous cBTKi treatment tend to develop selection or outgrowth of resistant clones, which triggers disease relapse. Non-covalent binding BTKi has become a treatment option for patients who progressed on cBTKi. LP-168 is a highly selective next-generation inhibitor of BTK that can bind wild-type BTK covalently and C481-mutated BTK non-covalently (reversibly) Here, we propose to evaluate the safety and efficacy of LP-168 monotherapy in patients with R/R MCL. Methods: NCT05716087 is an open-label, multicenter, single-arm, phase II study to assess the efficacy, safety, tolerability, and pharmacokinetics of LP-168 in Chinese patients with R/R MCL who have failed prior cBTKi treatment. Responses were evaluated using Lugano 2014 criteria. Eligible patients with R/R MCL must show evidence of disease progression or intolerance to at least a prior cBTKi. Patients are also required to have adequate bone marrow, liver function, kidney function, and heart function, and an ECOG performance status of 0-2. Moreover, patients must have at least one measurable lesion. Key exclusion criteria include previous non-covalent BTKi or BTK proteolysis-targeting chimeras (PROTAC) treatment, uncontrolled systemic disease, active infection, central nervous system (CNS) involvement, prior history of other malignancies within two years, and current pregnancy or breastfeeding. Concomitant use of strong or moderate CYP3A4 inducers and inhibitors or OATP1B1/OATP1B3 sensitive substrates is prohibited. LP-168 is orally administered at 150mg once daily in 28-day/cycle until progressive disease (PD), unacceptable toxicity, withdrawal of consent, death, or other reasons for treatment discontinuation. In this study, the primary endpoint was ORR according to an independent review committee (IRC) assessment based on the best overall response (BOR) of PR or better per Lugano 2014 criteria. Secondary endpoints include safety evaluation, quality of life assessment, PK parameters, ORR by investigator’s assessment, and other efficacy parameters, such as complete response ratio (CRR), progression-free survival (PFS), overall survival (OS), duration of response (DOR), and time to response (TTR). First patient was enrolled on May 12, 2023. Currently 41 study sites across China are actively enrolling patients. ClinicalTrials.gov Identifier: NCT05716087. Clinical trial information: NCT05716087 .