The novel fourth-generation BTK inhibitor rocbrutinib (LP-168) elicited durable responses in patients with relapsed/refractory mantle cell lymphoma (MCL) who had previously received a covalent BTK inhibitor, according to updated results from the phase 2 ROCK-1 trial (NCT05716087) presented at the
Findings showed that at a data cutoff of January 5, 2026, and a median follow-up of 19.49 months (range, 0.62-28.65), evaluable patients treated with rocbrutinib (n = 61) achieved an objective response rate (ORR) of 63.9% (95% CI, 50.6%-75.8%) by independent review committee (IRC) assessment, including a complete response (CR) rate of 23.0%. Investigator assessment produced a similar ORR at 62.3% (95% CI, 49.0%-74.4%), with a CR rate of 26.2%.
The median duration of response (DOR) was 16.46 months (95% CI, 8.25-not evaluable [NE]) per IRC assessment, and the median progression-free survival (PFS) was 7.39 months (95% CI, 3.71-18.30). Per investigator assessment, the median DOR and PFS were 16.46 months (95% CI, 5.55-22.14) and 5.52 months (95% CI, 3.71-12.68), respectively.
The median overall survival (OS) was not reached (95% CI, 15.97-NE) at a median follow-up of 23.36 months, with an estimated 24-month OS rate of 61.4% (95% CI, 47.9%-72.5%).
“[The] ROCK-1 study demonstrates that rocbrutinib, as a fourth-generation BTK inhibitor, is a [potential] new treatment option for patients with relapsed/refractory MCL previously treated with a covalent BTK inhibitor,” lead study author Yuqin Song, MD, of Peking University Cancer Hospital & Institute in Beijing, China, and colleagues wrote in a poster presentation of the data. “With extended follow-up, rocbrutinib still showed durable efficacy and favorable safety.”
Rocbrutinib is a fourth-generation BTK inhibitor that combines covalent (non-reversible) and noncovalent (reversible) binding mechanisms. Although covalent BTK inhibitors have become staples of MCL management, treatment options following progression on a covalent BTK inhibitor remain limited.2
ROCK-1 was a single-arm, multicenter, open-label, phase 2 pivotal study evaluating rocbrutinib in Chinese patients with relapsed/refractory MCL who progressed on or after, or were intolerant to, prior covalent BTK inhibitor therapy.1
Enrolled patients received oral rocbrutinib at 150 mg once per day until disease progression or unacceptable toxicity.
The primary end point was IRC-assessed ORR per Lugano 2014 criteria; secondary end points included DOR, PFS, OS, and safety.
From May 17, 2023, to June 5, 2024, 62 patients were enrolled and received at least 1 dose of rocbrutinib; 61 patients with centrally confirmed MCL were included in the baseline and efficacy analyses. The median treatment duration was 168 days (range, 9-813), and the maximum number of 28-day cycles received was 29.
Among the 61 evaluable patients, the median age was 61 years (range, 37-79), 19.7% had blastoid or pleomorphic histology, 68.9% had a baseline Ki-67 proliferation index of at least 30%, and 90.2% had Ann Arbor stage IV disease. Additionally, 62.3% had intermediate- or high-risk disease per simplified MCL International Prognostic Index criteria, and 62.3% had bulky disease. Patients had received a median of 3 prior lines of therapy (range, 1-10). All had prior covalent BTK inhibitor exposure, 95.1% had received a prior anti-CD20 antibody, 31.1% had received an immunomodulator, and 9.8% had received a BCL2 inhibitor.
The safety profile of rocbrutinib remained manageable with longer follow-up. Dose interruptions due to treatment-emergent adverse effects (TEAEs) occurred in 35.5% of patients, most commonly attributed to pneumonia (11.3%) and pyrexia (6.5%). Most treatment interruptions did not require dose modification, and the dose reduction rate was 3.2%. No TEAEs led to permanent treatment discontinuation or death.
The most common any-grade TEAEs occuring in at least 20% of patients included thrombocytopenia, anemia, neutropenia, increased white blood cell counts, increased lymphocyte count, increased creatinine level, and hyperuricemia. Grade 3 or higher TEAEs occurring in at least 5% of patients included increased lymphocyte count, infectious pneumonia, anemia, neutropenia, and thrombocytopenia.
