Rocbrutinib Shows Durable Efficacy in BTK Inhibitor–Pretreated R/R Mantle Cell Lymphoma

Rocbrutinib (LP-168) generated durable responses and prolonged survival in Chinese patients with relapsed/refractory mantle cell lymphoma (MCL) who had previously received a covalent BTK inhibitor (cBTKi), according to updated findings from the phase 2 ROCK-1 trial (NCT05716087) presented in a poster session at the 2026 EHA Congress.¹

At a data cutoff date of January 5, 2026, rocbrutinib induced an overall response rate (ORR) of 63.9% (95% CI, 50.6%-75.8%) by independent review committee (IRC) assessment, which included a complete response (CR) rate of 23.0%, among evaluable patients (n = 61). Per investigator assessment, the ORR with the drug was 62.3% (95% CI, 49.0%-74.4%) with a CR rate of 26.2%.

Moreover, after a median follow-up of 11.27 months (95% CI, 8.41-14.03), the median duration of response (DOR) was 16.46 months (95% CI, 8.25-not evaluable [NE]) per IRC assessment and 16.46 months (95% CI, 5.55-22.14) per investigator assessment. The median time to response was 1.84 months and 1.86 months, respectively.

"The ROCK-1 study demonstrates that rocbrutinib, as a fourth-generation BTKi, is a new treatment option for patients with R/R MCL previously treated with cBTKi," the study authors, led by presenting author Yuqin Song, MD, wrote in the poster. Song is a professor in the Department of Lymphoma at Peking University Cancer Hospital & Institute in Beijing, China.

Why do new treatment options matter in relapsed/refractory mantle cell lymphoma after covalent BTK inhibitor therapy?

MCL is a rare, clinically heterogeneous subtype of B-cell non-Hodgkin lymphoma. cBTKis have become a key component of treatment in the relapsed/refractory setting and are increasingly moving into frontline use. Nonetheless, disease progression on or intolerance to these agents remains common, and patients who have a cBTKi fail face limited therapeutic options and poor outcomes, with a historical median overall survival (OS) of under 10 months.² The noncovalent BTK inhibitor pirtobrutinib (Jaypirca) has partly addressed this gap; for example, in the pivotal phase 1/2 BRUIN trial (NCT03740529), pirtobrutinib elicited an ORR of 57.8% (95% CI, 46.9%-68.1%) with a 20.0% CR rate and a median DOR of 21.6 months (95% CI, 7.5-not reached) among the first 90 cBTKi-pretreated patients with MCL.

Rocbrutinib is a fourth-generation BTK inhibitor that combines covalent and noncovalent binding and retains activity against wild-type and C481-mutant BTK.^1,3 Initial ROCK-1 findings were reported at the 2025 ASH Annual Meeting,³ and in June 2026, the agent received accelerated approval from China's National Medical Products Administration for adult patients with R/R MCL who had received at least 2 prior systemic therapies, including a BTK inhibitor.⁴

The EHA analysis extends follow-up of the registrational cohort.¹

How was the ROCK-1 trial designed?

ROCK-1 is a single-arm, multicenter, open-label, phase 2 pivotal study examining rocbrutinib in Chinese patients with R/R MCL who had progressed on or after, or were intolerant to, previous cBTKi therapy. Eligible patients had MCL with a measurable lesion and prior BTK inhibitor exposure, and received oral rocbrutinib at a once daily dose of 150 mg on a 28-day cycle until disease progression or unacceptable toxicity. The primary end point was IRC-assessed ORR per Lugano 2014 criteria. Secondary end points included DOR, progression-free survival (PFS), OS, and safety, with adverse effects graded according to Common Terminology Criteria for Adverse Events version 5.0 criteria.

Between May 17, 2023, and June 5, 2024, a total of 62 patients were enrolled and received at least 1 dose of rocbrutinib; 61 were histologically confirmed to have MCL by central laboratory review and thus were included in the baseline and efficacy analyses. As of the data cutoff date, the median treatment duration across all 62 patients was 168 days (range, 9-813), and the maximum number of cycles received was 29.

The baseline characteristics, which were previously reported at the 2025 ASH Annual Meeting,^1,3 reflected a heavily pretreated, high-risk population: 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%, 90.2% had Ann Arbor stage IV disease, and 62.3% had intermediate- or high-risk disease by simplified MCL International Prognostic Index score. Patients had received a median of 3 prior lines of therapy (range, 1-10), and all had received a prior cBTKi (100%); 95.1%, 31.1%, and 9.8% of patients had prior anti-CD20 antibody, immunomodulator, or BCL-2 inhibitor (9.8%) exposure.

What additional efficacy and survival outcomes were reported with rocbrutinib in ROCK-1?

Responses were rapid and deep across both assessments. Best responses per IRC included CR in 23.0% of patients, partial response (PR) in 41.0%, stable disease in 6.6%, and progressive disease in 23.0%; corresponding investigator assessment rates were 26.2%, 36.1%, 11.5%, and 19.7%.

The median PFS was 7.39 months (95% CI, 3.71-18.30) per IRC and 5.52 months (95% CI, 3.71-12.68) per investigator assessment. After a median follow-up of 23.36 months (95% CI, 20.73-24.15), the median OS was not reached (95% CI, 15.97-NE), with 60.7% of patients alive and an estimated 24-month OS rate of 61.4% (95% CI, 47.9%-72.5%).

What did the safety analysis show with rocbrutinib in patients with R/R MCL?

The safety profile remained manageable with longer follow-up. Approximately 35% of patients experienced a dose interruption due to treatment-emergent adverse effects (TEAEs), most commonly pneumonia (11.3%) and pyrexia (6.5%). The majority of interruptions did not require dose modification; the dose reduction rate was 3.2%. No TEAEs resulted in permanent treatment discontinuation or death.

The most common any-grade TEAEs reported in at least 20% of patients included thrombocytopenia, anemia, neutropenia, increased white blood cell count, increased lymphocyte count, increased creatinine, hyperuricemia, and decreased white blood cell count. Grade 3 or higher TEAEs occurring in at least 5% of patients were increased lymphocyte count, infectious pneumonia, anemia, neutropenia, and thrombocytopenia.

"With extended follow-up, rocbrutinib still showed durable efficacy and favorable safety in patients with R/R MCL," the authors concluded.

References

1. Song Y, Cai Q, Tang X, et al. Updated efficacy and safety results of rocbrutinib from the phase 2 ROCK-1 study in patients with relapsed or refractory mantle cell lymphoma and previously treated with BTK inhibitor. Presented at: 2026 European Hematology Association Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PF945.
2. Wang ML, Jurczak W, Zinzani PL, et al. Pirtobrutinib in covalent Bruton tyrosine kinase inhibitor pretreated mantle-cell lymphoma. J Clin Oncol. 2023;41(24):3988-3997. doi:10.1200/JCO.23.00562
3. Song Y, Cai Q, Tang X, et al. Efficacy and safety of rocbrutinib, the fourth generation Bruton's tyrosine kinase inhibitor, in patients with BTK inhibitor pre-treated relapsed or refractory mantle cell lymphoma: results from a phase II ROCK-1 trial. Blood. 2025;146(suppl 1):886. doi:10.1182/blood-2025-886
4. Lupeng Pharmaceutical's fourth-generation BTK inhibitor rocbrutinib approved in China for relapsed or refractory mantle cell lymphoma. News release. Lupeng Pharmaceutical; June 4, 2026. Accessed June 15, 2026. https://www.prnewswire.com/news-releases/lupeng-pharmaceuticals-fourth-generation-btk-inhibitor-rocbrutinib-approved-in-china-for-relapsed-or-refractory-mantle-cell-lymphoma-302791348.html