In recent years, with the rapid development of immunotherapeutic agents such as bispecific antibodies, the treatment landscape of acute lymphoblastic leukemia has entered a new era of hope. At the 2025 Annual Meeting of the American Society of Hematology (ASH), research led by Professor Wang Ying from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, was selected for an oral presentation. The study reported updated results of the novel CD19×CD3 T-cell engager MK-1045 in adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). Hematology Frontier invited Professor Wang Ying for an in-depth interpretation of the study and a discussion of its future clinical prospects.Hematology Frontier: In your oral presentation, you introduced the novel CD19×CD3 bispecific T-cell engager MK-1045. Could you briefly describe the background of this study and the potential advantages of MK-1045 compared with existing therapies?
Professor Wang Ying: MK-1045 is a novel CD3/CD19 bispecific antibody with a new molecular structure. Previously, the classical CD3/CD19 bispecific antibody blinatumomab demonstrated superior efficacy compared with conventional chemotherapy in patients with relapsed/refractory acute lymphoblastic leukemia. However, blinatumomab has a short half-life of approximately two hours and requires continuous intravenous infusion for 24 hours a day over 28 days, which limits convenience and may adversely affect patients’ quality of life.
Although MK-1045 also targets CD3 and CD19, it is not composed solely of two single-chain variable fragments (scFvs). Instead, an Fc fragment has been incorporated on the basis of scFv, forming a full-length antibody molecule. Due to the increased molecular weight and Fc-mediated pharmacokinetics, the half-life of MK-1045 is significantly prolonged. Based on this pharmacokinetic advantage, MK-1045 can be administered once weekly, offering clear benefits in terms of dosing convenience and healthcare resource utilization compared with continuous infusion regimens.
In addition, clinical trial results have shown more encouraging efficacy signals with MK-1045, suggesting its strong potential for further development and application in the treatment of relapsed/refractory acute lymphoblastic leukemia.
Hematology Frontier: The study showed that at the 20 mg and 90 mg dose levels, the CR/CRi/CRh rate reached 92%, with most patients achieving MRD negativity. Could you comment on the efficacy differences observed across dose levels and how you assess the dose-dependency of MK-1045?
Professor Wang Ying: We are currently conducting a phase I clinical trial, which remains in the dose-escalation stage and aims to determine the recommended phase II dose (RP2D). To date, nine dose cohorts have been completed, with doses up to 90 mg, enrolling a total of 75 patients. Across the entire population, the overall response rate reached 55%.
Notably, as the dose increased, particularly at doses of 60 mg or higher, the response rate rose significantly. In the 90 mg dose cohort, the response rate reached 92%, and among responding patients, 91% achieved minimal residual disease negativity.
This is precisely the objective of the phase Ib study, which is to identify the dose that offers the optimal balance between safety and efficacy for subsequent phase II trials. Current data suggest that the 90 mg cohort performs particularly well. However, the phase Ib study is still ongoing, and we look forward to further defining the most appropriate RP2D and confirming these efficacy results in phase II studies.
Hematology Frontier: MK-1045 demonstrated significant efficacy even in patients previously treated with blinatumomab or CAR-T therapy. What do you see as the key advantages of MK-1045 in these high-risk, refractory patients, and what patient characteristics may benefit most?
Professor Wang Ying: As an antibody-based therapy, MK-1045 belongs to a later generation of immunotherapeutic development. Currently, several immunotherapies have already been approved, including blinatumomab, inotuzumab ozogamicin, and CAR-T cell therapies. Therefore, our study included patients who had previously received immunotherapy.
In the higher-efficacy target dose cohorts, namely doses of 60 mg or above, although patient numbers were limited, we observed that patients who had failed prior therapies could still benefit. Two patients previously treated with blinatumomab both achieved remission and MRD negativity. Additionally, three patients previously treated with CAR-T therapy all responded, with two achieving MRD negativity.
These findings indicate that MK-1045 retains efficacy in high-risk, heavily pretreated patients who have failed prior immunotherapies. This significantly strengthens our confidence that, if approved, MK-1045 could offer an important additional treatment option. As immunotherapy choices continue to expand, efficacy, safety, dosing convenience, and economic accessibility will become increasingly critical factors in clinical decision-making.
Hematology Frontier: As RP2D determination progresses, how do you envision the future clinical positioning of MK-1045 in adult R/R B-ALL? Are there plans to explore combination strategies or expand into other B-cell malignancies?
Professor Wang Ying: Based on the promising results from the phase Ib study, we are confident that MK-1045 will successfully advance into phase II and potentially phase III clinical trials. Regarding indication expansion, blinatumomab provides an important precedent. It was initially approved for relapsed/refractory patients, later expanded to MRD-positive disease, and has now even gained approval for MRD-negative indications.
Given the strong efficacy of MK-1045 in relapsed/refractory patients, along with its favorable safety profile and convenient administration, it is reasonable to anticipate that its indications may gradually expand to include MRD-positive patients and eventually become integrated into the full treatment course of acute lymphoblastic leukemia, including frontline therapy.
Furthermore, since MK-1045 targets CD19, a key antigen widely expressed in B-cell malignancies such as lymphoma, its development potential extends well beyond ALL. CAR-T therapies targeting CD19 have already achieved remarkable success in this area. Therefore, as a bispecific antibody, MK-1045 holds substantial promise for further development and indication expansion in B-cell lymphomas.
Expert Biography
Professor Wang Ying
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences
Director, Immunocyte Therapy Center & International Diagnosis and Treatment Center Chief Physician, MD, PhD Supervisor
National Advanced Worker in the Health System Distinguished Medical Talent of Tianjin
Standing Committee Member and Secretary-General, Chinese Society of Clinical Oncology (CSCO) Leukemia Expert Committee
Head, Leukemia Immunocyte Therapy Collaborative Group, China Hematologic Disease Specialty Alliance
Standing Committee Member, 6th Hematologic Malignancies Committee, Chinese Anti-Cancer Association
Standing Committee Member, Leukemia Committee, Chinese Medical Education Association
Committee Member, Cell and Gene Therapy Branch, Chinese Society for Cell Biology
Committee Member, Hematologic Rehabilitation Committee, Chinese Association of Rehabilitation Medicine
Board Member, Tianjin Society of Hematology and Regenerative Medicine
Editorial Board Member, Chinese Journal of Hematology and Leukemia & Lymphoma
Postdoctoral Fellow, Winship Cancer Institute, Emory University
Main research focus on leukemia and immunocyte therapy, including both clinical and basic research.
