The novel, highly selective next-generation Bruton's tyrosine kinase (BTK) inhibitor LP-168 is currently being evaluated in the phase 2 ROCK-1 trial (NCT05716087) as a monotherapy for patients with relapsed or refractory mantle cell lymphoma (MCL) in China. The open-label, single-arm, multicenter study is assessing the agent's safety and efficacy in patients who have previously been treated with covalent BTK inhibitors.
Overcoming BTK Inhibitor Resistance
Resistance and intolerance to covalent BTK inhibitors are major factors in treatment failure for MCL patients. Approved covalent BTK inhibitors like ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) have shown efficacy in relapsed/refractory MCL, but resistance remains a challenge. LP-168 is designed to address this issue with its ability to act as a covalent BTK inhibitor by irreversibly inhibiting BTK wild type, while also overcoming the resistance of covalent BTKs inhibitor due to its non-covalent binding and reversible inhibition of BTK C481 mutations.
ROCK-1 Trial Details
The ROCK-1 trial is enrolling patients with MCL who have measurable lesions and have previously been treated with a covalent BTK inhibitor. Additional inclusion criteria include disease progression or intolerance to at least one prior covalent BTK inhibitor, adequate organ function, and an ECOG performance status of no more than 2. Patients who have previously been treated with a noncovalent BTK inhibitor are excluded from the study.
Sixty-two patients will be enrolled and receive oral LP-168 at a dose of 150 mg once daily in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met.
The primary endpoint of the study is objective response rate (ORR) per Lugano criteria, as assessed by an independent review committee. Secondary endpoints include safety, quality of life, pharmacokinetics, and other efficacy parameters including investigator-assessed ORR, complete response ratio, progression-free survival, overall survival, duration of response, and time to response.
Enrollment and Study Sites
The first patient was enrolled in the ROCK-1 clinical trial on May 12, 2023, in China. Currently, there are 41 study sites across the country actively enrolling patients.
