News & Events
The American Society of Hematology (ASH) Annual Meeting and Exposition is one of the largest academic conferences in the field of hematology, showcasing the most cutting-edge research advancements and the latest drug development data from around the world. The 67th ASH Annual Meeting was held from December 6–9, 2025, in Orlando, Florida, USA.
At this conference, updates on clinical studies for Rocbrutinib (LP-168) and LP-118 were presented as types of oral presentation, abstract and poster. The complete abstracts are available on ASH website.
1. Presentation ID: 886
Title: 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
Session Type: Oral presentation
Speaker information: Yuqin Song, MD, Peking University Cancer Hospital & Institute, Beijing, China,
Room: OCCC - Tangerine Ballroom F1
Date: Monday, December 8, 03:30 PM - 03:45 PM EST
Part of session: 623. Mantle Cell, Follicular, Waldenstrom's, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Single Agent and Combination therapy for MCL
Abstract: abs25-7939
Abstract highlight:
Patients with relapsed or refractory mantle cell lymphoma (r/r MCL) following prior covalent Bruton tyrosine kinase inhibitor (cBTKi) therapy face extremely poor outcomes, characterized by unsatisfactory response and dismal survival. This population represents a substantial unmet clinical need in the field of hematologic malignancies, highlighting an urgent need for novel agents. Rocbrutinib is a novel, highly selective, the fourth generation covalent (non-reversible) and non-covalent (reversible) BTKi. It showed dual effects on both wild-type and C481 and some other mutant BTKs, and promising efficacy and favorable safety in multiple types of B cell non-Hodgkin lymphoma in a phase I study (ASH 2023).
Here we report the safety and efficacy of Rocbrutinib in Chinese heavily pre-treated r/r MCL patients with prior covalent BTK inhibitors from the phase II ROCK-1 study (NCT05716087).
Methods: The ROCK-1 trial (LP-168-CN201) is a single-arm, multicenter, open-label phase II study conducted across 27 study centers in China. Eligible adult cBTKi pre-treated r/r MCL patients received oral Rocbrutinib at 150 mg once daily (QD) until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR) assessed by independent review committee (IRC) per Lugano 2014 criteria.
Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Adverse events (AEs) were graded per CTCAE v5.0.
Results: Between May 2023 and June 2025, 61 centrally confirmed r/r MCL patients were enrolled, of which 19.7% patients have blastoid or pleomorphic histology. The median age was 61 years (range, 37-79), 73.8% was male, 62.2% with intermediate- or high-risk simplified MCL International Prognostic Index score (sMIPI), and 68.9% have high baseline ki-67 level (≥30%). The median number of prior therapies was 3 (range, 1- 10), including cBTK inhibitor (100%), anti-CD20 antibody (95.1%), immunomodulator (31.1%), BCL-2 inhibitor (9.8%), and stem cell transplant (6.6%). The median number of prior cBTKi treatment was 1 (range, 1-4), with 34.4% received more than two lines of prior cBTKi regimens. Per IRC’s assessment, the ORR was 63.9% (95% CI, 50.6-75.8), including 23.0% complete response. The median PFS was 7.39 months (95% CI, 3.71-18.30). At a median follow-up of 11.27 months, the median DOR was 16.46 months (95% CI, 8.25-not reached), with the 12-month estimated DOR rate was 61.2%. After a median follow-up of 17.02 months (range, 14.78-18.46), median OS was not reached. The rate of AEs of special interest related to BTKi was less frequent, with major bleeding (Grade ≥3 hemorrhage) of 3.2% and no atrial fibrillation or flutter of any grade was reported. Dose interruptions due to TEAEs occurred in 33.9% of patients, while only 3.2% required dose reduction. There was no permanent discontinuation of Rocbrutinib treatment or death attributed to TEAEs.
Conclusions: Rocbrutinib demonstrated clinically meaningful and durable efficacy with a manageable safety profile in heavily pretreated, cBTKi-exposed Chinese r/r MCL patients. The high ORR (63.9%) and prolonged DOR (median 16.46 months) observed in this trial, coupled with a low incidence of BTKi-associated toxicities, position Rocbrutinib as a promising therapeutic option for this difficult-to-treat population. The clinical benefit of Rocbrutinib in patients with MCL will be further confirmed in randomized phase III studies.
ASH website link: https://submit.hematology.org/program/presentation/672013
2.Presentation ID: 87
Title: Updates of R/R CLL with prior exposure to Bruton’s tyrosine kinase (BTK) inhibitor and/or bcl-2 inhibitor in the Phase 1 trial of LP-168 (Rocbrutinib), a novel COVALENT and non-COVALENT BTK inhibitor
Session-Type: Oral Abstract Session
Speaker information: Jennifer Woyach, MD, The Ohio State University, Columbus, OH, United States
Room: OCCC - W224ABEF
Date: Saturday, December 6, 10:00 AM - 10:15 AM EST
Part of session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Treatment of CLL in Relapse and in Richter Transformation
Abstract: abs25-2620
Abstract highlight:
LP-168 (Rocbrutinib) is a new selective next-generation inhibitor of BTK that broadly targets wild-type (WT) BTK irreversibly, C481 mutant BTK (C481S, C481F, and C481R) reversibly, and other non- C481 mutations in relapsed/refractory (R/R) CLL. R/R CLL that has been treated with prior BTKi and/or Bcl- 2 inhibitor, such as venetoclax, remains an unmet need in resistant CLL despite Pirtobrutinib's accelerated approval. Resistance to Pirtobrutinib—often through non-C481 BTK mutations—can limit durability of response, and outcomes in double-exposed patients remain poor. Below, we describe the updated safety and efficacy results of R/R CLL with prior exposure to BTKi and/or Bcl-2 inhibitor in the Rocbrutinib phase 1 trial (NCT04775745).
Methods: NCT04775745 is a multicenter phase 1 dose escalation study of Rocbrutinib monotherapy in pts with R/R B-cell malignancies. Overall response rate (ORR) included patients with complete response (CR), partial response (PR), or partial response with lymphocytosis (PR-L).
Results: From 16 Sep 2021 to 28 Mar 2025, 42 post-BTKi R/R CLL pts (including 19 post-BTKi/Bcl-2i pts) were enrolled. The median age was 66 years (range, 45–81), and 83.3% of the participants were male. Post- BTKi CLL patients had 4 median prior therapies (range, 2-9), with 45.2% receiving more than one prior cBTKi and 21.4% receiving both cBTKi(s) and ncBTKi(s). 31 pts (31/33, 93.9%) had unmutated IGHV, 12 pts (12/39, 30.8%) had complex karyotype, 24 pts (24/41, 58.5%) had Del(17p) and/or TP53 mutation, 17 pts (17/42, 40.5%) had Del11q, 26 pts (26/40, 65.0%) had C481S BTK mutations and 7 (7/40, 17.5%) pts had C481F/Y/R/V BTK mutation, 12 pts (12/39, 30.8%) had gatekeeper mutations at T474 BTK, 2 pts (2/39, 5.1%) had BTK L528W mutation, 1 pt (1/39, 2.6%) had BTK A428D mutation, 1 pt (1/39, 2.6%) had BTK V416L mutation and 4 pts (4/39, 10.3%) had a resistance mutation inPLCγ2.
As of 28 March 2025, 40 post-BTKi CLL pts have available response data with median duration of treatment (DOT) of 22.4 months (range 2.8, 42.1). ORR with dose levels (DLs) of 200mg daily and 300mg daily was 78.3% (18/23), with 16 pts of PR and 2 pts of PR-L. Of the 40 CLL patients by the data cutoff date, estimated median progression-free survival (PFS) is 28.1 months (95%CI 17.58, NE) with the median follow-up of 30.3 months (95%CI 24.5, 38.8), and estimated median duration of response (DOR) is not reached (95%CI 19.42, NE). 19 pts (19/42, 45.2%) remained on therapy.
Among the 40 post-BTKi CLL pts, 17 pts were also exposed to Bcl-2i venetoclax. ORR in DLs 200-300mg daily being 80.0% (8/10). Among the 17 pts, 4 pts were exposed to cBTKi, ncBTKi, and Bcl-2i, and in these pts ORR with all DLs was 50.0% (2/4) and was 100.0% (2/2) for pts treated at the 300mg DL. Best response for the remaining 2 pts (2/4) that did not respond was both stable disease (SD).
All 42 post-BTKi CLL patients were evaluated for safety. Most AEs have been low grade.
Conclusions: Encouraging safety and efficacy are observed in the population exposed to BTKi (including both cBTKi and ncBTKi) and/or Bcl-2i. Rocbrutinib could be a potential therapy for double or triple- exposed CLL patients who currently have limited treatment options.
ASH website link: https://submit.hematology.org/program/presentation/678827
3. Presentation ID: 3587
Title: Efficacy and safety of Rocbrutinib, a highly selective 4th-generation Bruton’s tyrosine kinase inhibitor, in relapsed/refractory Mantle Cell Lymphoma (R/R MCL): Updated results from the phase 1 study
Session-Type: Poster Abstract Session
Speaker information: Yuqin Song, MD, Peking University Cancer Hospital & Institute, Beijing, China
Room: OCCC - West Halls B3-B4
Date: Sunday, December 7, 06:00 PM - 08:00 PM EST
Part of session: 623. Mantle Cell, Follicular, Waldenstrom's, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Abstract: abs25-8511
Abstract highlights:
The advent of novel targeted and immunotherapeutic approaches, particularly Bruton’s tyrosine kinase inhibitors (BTKis), have significantly improved survival outcomes in patients with mantle cell lymphoma (MCL), with acceptable safety profiles. However, therapeutic challenges (e.g. acquired resistance, intolerance, etc.) remain. Rocbrutinib is a highly selective, 4th-generation BTKi that integrates the advantages of covalent irreversible inhibition and non-covalent binding and demonstrates superior pharmacokinetic profiles in humans. Previously, data have demonstrated that Rocbrutinib induces high response rate and durable responses in heavily pre-treated patients with R/R MCL, particularly those with prior BTKi exposure (Yuqin Song et al. 2023 ASH). Here, we present updated data from the ongoing phase I trial LP-168-CN101 (NCT04993690) evaluating Rocbrutinib in patients with BTKi naïve R/R MCL.
Methods: Patients aged 18–80 with R/R MCL who had received ≥1 line of therapies (including ≥1 line anti-CD20 antibody-based regimens) were treated with Rocbrutinib monotherapy until disease progression. Adverse events (AEs) were graded per CTCAE v5.0, and efficacy was assessed per Lugano 2014 criteria.
Results: As of June 15, 2025, 28 BTKi-naïve R/R MCL patients were enrolled and received Rocbrutinib 100 mg (n=4), 150 mg (n=23), or 200 mg (n=1) once daily (QD) treatment. The median age was 61 years (range: 40–77). Blastoid/pleomorphic variants accounted for 17.9% of cases, and 45.7% of patients were with intermediate- or high-risk per MCL international prognostic index (MIPI). The median number of prior lines of therapies was 1 (range: 1-3), with 14.3% of patients having undergone autologous stem cell
transplantation.
Of 28 efficacy evaluable patients, the overall response rate (ORR) was 89.3%, with a complete response (CR) rate of 57.1%. After median follow-up of 21.2 (range: 0.9-43.1) months, PFS is not matured yet. The 18-month PFS rate was 74.3%. There was no permanent discontinuation of Rocbrutinib treatment or death attributed to TEAEs.
Conclusion: Consistent with previously reported data in patients with post BTKi R/R MCL, Rocbrutinib demonstrates a favorable safety profile and robust efficacy in patients with BTKi naïve R/R MCL, with high response rates, deep remissions, and durable responses.
ASH website link: https://submit.hematology.org/program/presentation/675632
4. Presentation ID: 3896
Title: Efficacy and safety of Rocbrutinib, a highly selective 4th-generation BTK inhibitor, in Chinese patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)
Session-Type: Poster Abstract Session
Speaker information: Yuqin Song, MD, Peking University Cancer Hospital & Institute, Beijing, China
Room: OCCC - West Halls B3-B4
Date: Sunday, December 7, 06:00 PM - 08:00 PM EST
Part of session: 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Poster II
Abstract: abs25-7975
Abstract highlight
Rocbrutinib, a highly selective, 4th-generation Bruton's tyrosine kinase (BTK) inhibitor, uniquely takes advantage of both covalent irreversible inhibition for wide-type BTK and non-covalent binding for C481- mutant variants. Here, we present the safety and efficacy results from the ongoing phase I trial (LP-168- CN101; NCT04993690) of Rocbrutinib in Chinese patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
Methods: Eligible patients aged 18–80 with a confirmed diagnosis of CLL/SLL were treated with Rocbrutinib monotherapy until disease progression or intolerable toxicity. Adverse events (AEs) were graded per CTCAE v5.0, and response was evaluated per 2018 iwCLL criteria.
Results: As of April 15, 2025, 41 (untreated (1L), n=12; relapsed/refractory (R/R) BTKi-naïve, n=17; R/R post-BTKi, n=12) CLL/SLL patients were enrolled and treated with Rocbrutinib (100 mg ,n=1; 150 mg, n=28; 200 mg, n=10; 300mg, n=2) once daily. The median age was 60 (range, 35-79) years. Of the patients with evaluable samples, 26.9% (7/26) with del(17p), 42.9% (12/28) with TP53 mutation, 63.0% (17/27) with unmutated IGHV and 44.0% (11/25) with complex karyotype. Of the 29 R/R CLL/SLL patients, the median number of prior therapies was 2 (range, 1-5), including prior covalent BTKis (34.5%), BCL2 inhibitors (BCL-2i, 24.1%), and noncovalent BTKis (6.9%). In R/R post-BTKi CLL/SLL patients, most (91.7%) discontinued prior BTKi due to disease progression; 41.6% had prior BCL-2i ; 6/9 (66.7%) carried BTK mutations, including BTKC481S, BTKC481Y/R and BTKL528W.
In 1L patients (n=12), the overall response rate (ORR, partial response with lymphocytosis or better) was 91.7%. The ORR and complete remission (CR)/CR with incomplete marrow recovery (CRi) rates in R/R BTKi-naïve patients (n=17) were 100% and 17.6%, respectively. In R/R post-BTKi patients, Rocbrutinib monotherapy achieved 75% ORR including16.7% CR/CRi. In BTKi and BCL-2i double refractory population (n=5), ORR and CR/CRi rates were 80.0% and 40.0%, respectively; 3 patients are still in remission while the other 2 patients both had durable responses of more than 17 months. 2 patients with BTKL528W mutation achieved PR and are still on treatment (DOR: 8.1 and 14.0 months). After median follow-up of 7.4 months, all 12 1L patients remained on treatment. In the R/R BTKi naive population (median follow-up 15.8 months), the estimated 12-month PFS rate as 94.1% (95% CI: 65.0- 99.1); In the R/R post-BTKi population (median follow-up 15.5 months), the estimated 12-month PFS rate as 83.3% (95% CI: 48.2-95.6).
Conclusion: Rocbrutinib has a favorable safety profile and shows durable responses in patients with CLL/SLL, including those with prior BTK inhibitor exposure and/or with covalent and noncovalent BTKi-resistant mutations.
ASH website link: https://submit.hematology.org/program/presentation/673463
5. Presentation ID: 1532
Title: Targeting BTKi-resistant CLL using the dual irreversible/reversible 4th generation BTK inhibitor Rocbrutinib
Session-Type: Poster Abstract Session
Speaker information: Britten Gordon, MD, The Ohio State University, Internal Medicine, Columbus, OH, United States
Room: OCCC - West Halls B3-B4
Date: Saturday, December 6, 05:30 PM - 07:30 PM EST
Part of session: 605. Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Poster I
Abstract: abs25-11446
Abstract Highlight:
Treatment of CLL has been transformed by targeted therapies including inhibitors of Bruton’s tyrosine kinase (BTKi). Currently, three covalent BTKi (cBTKi) are approved for CLL, but most patients eventually relapse, commonly through acquisition of the C481S BTK mutation (Woyach et al., 2014). Non-covalent BTKi (ncBTKi) retain activity against C481 mutations, but are susceptible to secondary BTK mutations (T474I, L528W, M437R, and V416L), which can also confer resistance to covalent BTKi (Wang et al., 2022). Regardless of these mutations, BCR signaling remains intact, suggesting that inhibition of the BCR pathway retains its therapeutic importance. Agents capable of targeting and inhibiting both wild-type (WT) and mutant BTK (C481S, T474I, and L528W) are ideal for treating CLL to retain BTK inhibition and prevent clinical relapse through the most common resistance mechanisms.
Rocbrutinib is a novel selective BTKi with an active warhead capable of binding both WT and mutant BTK.
Methods: Validation of covalent binding was performed by X-Ray co-crystallography. To confirm binding of Rocbrutinib to WT and mutant BTK, we performed a NanoBRET assay against WT, C481S, T474I, and L528W BTK. To further measure the binding affinity of Rocbrutinib and the currently available BTKi towards full-length WT and mutant BTK in HEK293T cells, we utilized a fluorescent probe cellular binding assay (FPCBA) (Yin et al., 2024). Using genetically modified TMD8 cells that express only C481S, T474I, or L528W mutated BTK, we determined the effect of Rocbrutinib on cell viability and BCR signaling. Primary CLL B-cells were isolated and treated with Rocbrutinib for all experiments. BCR signaling alterations were assessed via immunoblot to observe changes in target protein phosphorylation. In vivo studies were performed using Eμ-TCL1 and Eμ-MTCP1 mouse engraftment models.
Results: A crystal structure of BTK in complex with Rocbrutinib showed Rocbrutinib binds BTK in the ATP- binding site, forms a covalent bond to C481, and forms hydrogen bonds to M477, D539, and K430. In a NanoBRET assay, Rocbrutinib demonstrated low nanomolar binding affinity towards the WT, C481S, T474I, and L528W BTK proteoforms with IC50 values of 4.7, 49.7, 13.1, and 80.4 nM, respectively. Using FPCBA, Rocbrutinib was the only BTKi—among Ibrutinib, Acalabrutinib, Zanubrutinib, Nemtabrutinib, and Pirtobrutinib—to retain nanomolar potency against WT BTK as well as clinically relevant resistance mutations, including C481S, V416L, M437R, and L528W. In TMD8 cells, Rocbrutinib maintained nanomolar GI50 towards WT, C481S, T474I, and L528W BTK. Rocbrutinib also inhibited BCR signaling regardless of BTK mutation status demonstrated by reducing production of CCL3 (WT: 98.8%, p < 0.0001; C481S: 99.1%, p<0.0001; T474I: 98.9%, p<0.0001; L528W: 99.6%, p<0.0001) and CCL4 (WT: 97.3%, p<0.0001; C481S: 96.3%, p<0.0001; T474I: 97.3%, p<0.0001; L528W: 99.3%, p<0.0001) as well as inhibiting BTK, PLCγ2, ERK, and AKT activation. After two-hours of treatment, 500 nM Rocbrutinib inhibited BCR signaling in primary CLL B-cells, demonstrated by reduced phosphorylation of BTK (98.9%, p<0.0001), PLCγ2 (85.6%, p<0.0001), ERK (59.3%, p=0.0029), and AKT (68.9%, p=0.0014). Furthermore, we observed retained inhibition of BCR signaling in primary CLL B-cells harboring C481S BTK via immunoblotting and cytokine production. Finally, to evaluate the in vivo efficacy of Rocbrutinib, we evaluated its therapeutic impact in both the Eµ-TCL1 and Eµ-MTCP1 mouse models. We treated mice daily via oral gavage and found that 50 mg/kg of Rocbrutinib significantly improved survival in the Eµ-TCL1 model when compared to vehicle (median 51 vs 44 days; p=0.0018) or Ibrutinib at the same dose (median 51 vs 45 days; p=0.0098). Similarly, in the Eµ-MTCP1 model, Rocbrutinib (50 mg/kg) markedly improved survival relative to vehicle (median 122 vs 62 days; p<0.0001) or Ibrutinib at the same dose (median 122 vs 96 days; p=0.0162).
Conclusion: Collectively, our findings demonstrate Rocbrutinib is a potent and selective inhibitor of BTK with activity even in the presence of mutations that mediate resistance to cBTKi and ncBTKi. These data support the continued investigation of Rocbrutinib, which is currently being studied in the phase 1 setting of CLL and NHL (NCT04775745 and NCT04993690).
ASH website link: https://submit.hematology.org/program/presentation/678943
6. Presentation ID: 5136
Title: Trial in progress: A Phase I/II study to investigate the combination of LP-118, Ponatinib, vincristine and dexamethasone (LPVd regimen) in relapsed/refractory T-ALL/lbl
Session-Type: Poster Abstract Session
Speaker information: Caner Saygin, MD，University of Chicago, Chicago, IL, United States
Room: OCCC - West Halls B3-B4
Date: Monday, December 8, 06:00 PM - 08:00 PM EST
Part of session: 613. Acute Lymphoblastic Leukemias: Therapies Excluding Allogeneic Transplantation: Poster III
Abstract: abs25-12790
Abstract highlight:
Background and significance: T-lineage acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) accounts for 15% of pediatric and 25% of adult ALL cases. Precursor T-ALL and its more immature subset, early T precursor (ETP) ALL, have limited treatment options after first-line chemotherapy. Due to this unmet need, long-term survival for relapsed/refractory (R/R) T-ALL is
LP-118 is an oral dual BCL-2/BCL-xL inhibitor, with a modified structure and fine-tuned BCL-xL activity to minimize platelet toxicity. Based on our preclinical work showing the synergy between LP-118 and Ponatinib (pre-TCR signaling inhibitor), we designed the phase 1/2 LPVd trial combining LP-118 and Ponatinib (LCK inhibitor) with low-intensity chemotherapy backbone (Vd: vincristine, dexamethasone) in patients with R/R T-ALL/LBL (NCT06207123). The trial was activated at the University of Chicago in September 2024, and we plan to open it at four additional sites.
Study design and methods: Adult patients (≥18 years) with R/R T-ALL/LBL, defined as bone marrow or blood involvement with ≥5% lymphoblasts, or measurable residual disease (MRD) with >10-4 level detected by multiparameter flow cytometry or NGS-based MRD, or patients with isolated extramedullary disease that is measurable by CT scan are eligible. Participants should otherwise have good performance status (ECOG 0-2), adequate organ function, and no active infections.
In phase 1, a standard 3+3 design is implemented to test the combination of different dose levels of LP- 118 with low-intensity chemotherapy (Vd) at dose levels 1 (100 mg), 2 (200 mg) and 3 (300 mg), followed by the addition of Ponatinib 30 mg to different dose levels of LP-118 at levels 4 (100 mg), 5 (200 mg) and 6 (300 mg). Ponatinib dose reduction to 15 mg is allowed for participants who experience toxicity or achieve MRD-negative remission. The primary objective of the phase 1 portion is to identify the recommended phase 2 dose (RP2D) of this novel-novel combination therapy. The primary endpoint is dose limiting toxicity (DLT), defined as a grade ≥3 non-hematologic toxicity related to the study drugs, except for the following which will not be considered DLT: grade 3 fatigue, asthenia, fever, anorexia, constipation; grade 3 nausea, vomiting or diarrhea not requiring tube feeding, total parenteral nutrition or hospitalization; infection, bleeding or other expected direct complication of cytopenias due to active underlying leukemia. The maximum tolerated dose is the dose such that <33% of patients (<2 of 6) experience DLT.
ASH website link: https://submit.hematology.org/program/presentation/673229