Latest data of InnoCare’s (HKEX: 09969; SSE: 688428) robust oncology pipelines were presented at the ongoing European Hematology Association (EHA) 2025 Congress.

Poster Presentation: 

1. First Presentation of Efficacy and Safety Data for First-Line Treatment of CLL/SLL with BCL2 Inhibitor Mesutoclax in Combination with BTK Inhibitor Orelabrutinib (Abstract No.: PS1567)

The study showed that mesutoclax (100 and 125 mg) in combination with orelabrutinib was safe and well tolerated in patients with treatment na?ve (TN) CLL/SLL. Substantial efficacy was observed, with early high undetectable MRD (uMRD) rate.

42 patients with TN CLL/SLL were enrolled (mesutoclax 100 mg, n=21; 125 mg, n=21). The fixed-duration treatment of mesutoclax in combination with orelabrutinib is expected to deliver deeper remissions for TN CLL/SLL patients. In all patients, the overall response rate (ORR) was 97.6%.

At week 24 of the combination therapy, in the 125 mg dose cohort, the overall response rate (ORR) was 100%, the complete remission rate (CRR) was 23.8%, the CRR in target lesions was 57.1%, and the peripheral blood (PB) uMRD rate was 48%. In the 100 mg mesutoclax dose cohort, the ORR was 95.2%, the CRR was 19.0%, the CRR in target lesions was 42.9%, and the PB uMRD rate was 19%. With the extension of the duration of treatment, the therapeutic efficacy is expected to be further improved.

All patients are still on treatment. No disease progression or death occurred, and no adverse events leading to discontinuation of treatment were reported.

Due to its favorable efficacy and safety profile, a registrational Phase III clinical study of mesutoclax (125 mg once daily) in combination with orelabrutinib for the treatment of TN CLL/SLL patients has been initiated, with patient enrollment being accelerated.

2.Orelabrutinib Combined with Bendamustine-Rituximab or Obinutuzumab followed by Orelabrutinib Maintenance in Untreated Marginal Zone Lymphoma (OPTIMIZE): A Multicenter, Single-Arm, Phase II Study (Abstract No.: PF898)

The absence of a standard first-line treatment for marginal zone lymphoma (MZL) have inspired the exploration of novel regimens. In recent years, Bruton’s tyrosine kinase inhibitors (BTKis) have demonstrated durable responses with a favorable benefit-risk profile across all MZL subtypes in the relapsed/refractory setting. Orelabrutinib is a novel BTK inhibitor with higher selectivity and fewer off-target than other BTK inhibitors. Orelabrutinib combined with bendamustine-rituximab or obinutuzumab followed by orelabrutinib maintenance was effective and well-tolerated in untreated patients with MZL.

The majority of patients presented with MALT lymphoma and had Ann Arbor stage II-IV disease. At the end of induction treatment, the overall response rate (ORR) was 100.0% among all enrolled patients. At the data cutoff, the median progression-free survival (PFS) and overall survival (OS) remained immature. No BTK inhibitor-related adverse events (AEs), such as atrial fibrillation or bleeding, were observed.

3.The Rationality, Efficacy and Safety of Orelabrutinib plus Obinutuzumab (O2) in Systemic Treatment-na?ve Marginal Zone Lymphoma: A Prospective Cohort Study (Abstract No.: PS1902)

The Orelabrutinib plus Obinutuzumab regimen had well rationality and demonstrated promising efficacy.

Across the entire study and during the period of induction therapy, the best objective response rate (ORR) was 100%. 3 patients who achieved partial response (PR) after the induction therapy subsequently achieved complete response (CR) in the maintenance period. The 18-month progression-free survival (PFS) and overall survival (OS) rates were both 100%.

4.Ultra-low Dose Radiotherapy Combined with Orelabrutinib Improves the Complete Response Rate of Treatment for Localized Ocular Adnexal Extranodal Marginal Zone B-cell Lymphoma (Abstract No.: PS1901)

The combination of ultra-low dose radiotherapy and orelabrutinib in the treatment of ocular adnexal extranodal marginal zone lymphoma (OA-EMZL) not only improves the effectiveness of treatment but also significantly reduces the toxic effects of radiotherapy, providing a new approach for the treatment of localized OA-EMZL.

Of all the 17 patients who completed treatment, 16 patients achieved complete response (CR) and one patient achieved a partial response. Additionally, the lesions in the patients still undergoing treatment have shrunk compared to before treatment.

5.Orelabrutinib plus Bendamustine-Rituximab (OBR) versus Bendamustine-Rituximab (BR) in Transplant-ineligible, Intermediate- to High-risk Mantle Cell Lymphoma (MCL) (Abstract No.: PS1969)

This open-label, randomized, multi-center study aims to compare the efficacy and safety of Orelabrutinib plus Bendamustine-Rituximab versus Bendamustine-Rituximab in transplant-ineligible, intermediate- to high-risk mantle cell lymphoma (MCL) patients. Early data suggest that Orelabrutinib plus Bendamustine-Rituximab could reduce disease progression events compared to Bendamustine-Rituximab in high-risk MCL. Updated outcomes on efficacy, safety, and biomarker analysis will be reported.

6.Pomalidomide, Rituximab, Orelabrutinib, and MiniCHOP-like (PRO-miniCHOP) in Elderly Patients with Newly Diagnosed Diffuse Large B-cell Lymphoma: Updated Results from a Phase II Study (Abstract No.: PF950)

The results further support Pomalidomide, Rituximab, Orelabrutinib, and MiniCHOP-like (PRO-miniCHOP) as a potential treatment option for elderly patients with diffuse large B-cell lymphoma (DLBCL), demonstrating promising efficacy and acceptable safety, especially for those who responded to the Pomalidomide-Rituximab-Orelabrutinib (PRO) induction therapy.

A total of 32 patients were enrolled in this study, of whom 26 patients completed ≥3 cycles of the PRO-miniCHOP, resulting in a complete response rate (CRR) of 65.4% and overall response rate (ORR) of 100.0%. Among the 21 patients who completed the full 6-cycle therapy with PRO-miniCHOP, both the CRR and ORR were 95.2%. At a median follow-up of 15.6 months, the median progression-free survival (PFS) and overall survival (OS) had not yet been reached, with the 2-year PFS and OS rates being 94.7% and 100.0%, respectively.

7.Orelabrutinib Addition to R-CHOP-like Regimen Adapted to Response in Treatment-Na?ve Non-GCB DLBCL: Update Results of Orient Study (Abstract No.: PS1943)

In non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL) patients who responded to orelabrutinib plus rituximab (OR) induction, orelabrutinib plus R-CHOP-like (OR-CHOP) exhibited favorable antitumor activity and manageable safety. Update results further support the orelabrutinib plus R-CHOP-like therapy as an option in this disease. 

At end of 6-cycle orelabrutinib plus R-CHOP-like, response (all 100%) was independent of double-expressing lymphoma (DEL), extranodal involvement (EI), and Lymphgen subtypes. No off-target-related cardiac toxicities occurred.

8.Primary Efficacy and Safety of First-line R-MTO Regimen (Rituximab, Methotrexate, Thiotepa, and Orelabrutinib) followed by Autologous Hematopoietic Stem Cell Transplantation in PCNSL (Abstract No.: PF966)

The Rituximab, Methotrexate, Thiotepa, and Orelabrutinib (R-MTO) induction treatment has demonstrated notable efficacy in achieving higher response rate among patients with newly diagnosed primary central nervous system lymphoma (PCNSL), with a manageable safety profile. 

At the data cutoff, all patients had completed four cycles of induction therapy, and the complete response (CR) rate and overall response rate (ORR) were 93.34% and 96.67%, respectively. The 12-month progression-free survival (PFS) and overall survival (OS) rates were 82.26% and 85.33%, respectively.

9.Orelabrutinib, Rituximab Combined with High-Dose Methotrexate as Induction Therapy in Newly Diagnosed Primary Central Nervous System Lymphoma (Abstract No.: PS1917)

This study demonstrated the promising efficacy of the Orelabrutinib, Rituximab Combined with High-Dose Methotrexate induction regimen in newly diagnosed primary central nervous system lymphoma (PCNSL), with encouraging response rates and durable progression-free survival (PFS). The regimen also showed promising overall survival (OS) trends, highlighting its potential as an effective treatment. Treatment-related adverse events (TRAEs) were manageable, and no severe BTK inhibitor-related off-target toxicities (e.g., atrial fibrillation/flutter) were observed. These findings suggest that the Orelabrutinib, Rituximab Combined with High-Dose Methotrexate regimen is a well-tolerated and effective therapeutic option for PCNSL.

Except the above poster presentations, more than 10 studies were also selected as poster presentations or online publications at the meeting. For more detailed clinical data, please refer to EHA website.

About InnoCare

InnoCare is a commercial stage biopharmaceutical company committed to discovering, developing, and commercializing first-in-class and/or best-in-class drugs for the treatment of cancers and autoimmune diseases with unmet medical needs in China and worldwide. InnoCare has branches in Beijing, Nanjing, Shanghai, Guangzhou, Hong Kong, and the United States.

InnoCare Forward-looking Statements

This report contains the disclosure of some forward-looking statements. Except for statements of facts, all other statements can be regarded as forward-looking statements, that is, about our or our management's intentions, plans, beliefs, or expectations that will or may occur in the future. Such statements are assumptions and estimates made by our management based on its experience and knowledge of historical trends, current conditions, expected future development and other related factors. This forward-looking statement does not guarantee future performance, and actual results, development and business decisions may not match the expectations of the forward-looking statement. Our forward-looking statements are also subject to a large number of risks and uncertainties, which may affect our short-term and long-term performance.