MRG001 Shines at ASH: Prof. Song Yuqin Leads Pioneering Anti-CD20 ADC Study in Relapsed/Refractory B-cell Lymphoma
Editor’s Note: This article is republished from Today’s Oncology of the China Medical Tribune, with authorization granted to VCBeat for republication.
From December 11 to 14, 2021, the American Society of Hematology (ASH) Annual Meeting was successfully held. At this conference, the “Phase Ia Dose-Escalation Study of Anti-CD20 ADC MRG001 in Relapsed/Refractory Advanced B-Cell Non-Hodgkin Lymphoma,” led by Professor Song Yuqin from Peking University Cancer Hospital, was selected for the poster session. This presentation showcased the innovation of an originally developed ADC and Chinese intellectual contributions to the global medical community, marking the international debut of the anti-CD20 agent MRG001.
To this end, our journal has specially invited Professor Song Yuqin for an exclusive interview to provide readers with a detailed interpretation of the data and value of this study, as well as an analysis of the current treatment landscape for B-cell lymphoma, the research and development progress of anti-CD20 antibody-drug conjugates (ADCs), and the future prospects of MRG001. We cordially invite you to read the highlights of this interview!
Prof. Yuqin Song
Deputy Director, Department of Lymphoma; Chief Physician; Doctoral Supervisor, Peking University Cancer Hospital
Director of the Chinese Society of Clinical Oncology (CSCO)
Secretary-General, CSCO Anti-Lymphoma Alliance
Chairman, Lymphatic and Hematologic Oncology Professional Committee, Beijing Anti-Cancer Association
Vice Chair, Lymphoid and Hematologic Malignancies Committee, Chinese Society of Geriatric Oncology
Vice Chairman, Lymphoma Professional Committee of the China Association for Geriatric Health Care
Standing Committee Member and Secretary, Oncology Professional Committee, Beijing Medical Association
Exclusive Interview Video with Professor Song Yuqin
Q: Could you please share the original intention and background behind conducting this study? What was the design of the study protocol?
Professor Song Yuqin:CD20-targeted monoclonal antibodies have been used in the treatment of lymphoma for 20 years. Approximately two-thirds of patients with lymphoma have CD20-positive B-cell lymphoma, making CD20 one of the most promising therapeutic targets for drug development.
The most extensively utilized agents in this field to date have been naked monoclonal antibodies targeting CD20, such as rituximab. Multiple clinical studies have demonstrated that in the treatment of B-cell lymphomas, particularly diffuse large B-cell lymphoma (DLBCL), both the first-line CHOP and R-CHOP regimens can improve patient survival by 15% to 20%. However, in clinical practice, we have observed that some patients may exhibit resistance to CD20-targeted naked monoclonal antibodies due to the absence of the corresponding target in their bodies, while the majority experience suboptimal therapeutic efficacy owing to resistance mechanisms and other factors. Currently, numerous drug development efforts remain focused on the CD20 target, with antibody-drug conjugates (ADCs) representing one such approach.
Antibody-drug conjugates (ADCs) are biologically guided missiles composed of monoclonal antibodies linked to chemotherapeutic agents via linkers. Upon administration, they precisely bind to CD20-positive B-cell lymphomas, thereby achieving optimal therapeutic outcomes. This is also the core design principle behind MRG001: by conjugating a naked monoclonal antibody with the chemotherapeutic agent MMAE, it targets CD20-positive tumor cells in vivo, enabling precise localization and destruction of the tumors. To explore the safety and efficacy of MRG001 in humans, we designed a Phase Ia, single-arm, dose-escalation study, aiming to identify the effective and safe dosage ranges for future Phase II clinical trials. This was the original intent of our study design; overall, the current research has largely achieved its intended objectives.
Q: Please provide a detailed analysis of the efficacy and safety data from this study.
Professor Yuqin Song:The success or failure of Phase I clinical trials for antibody-drug conjugates (ADCs) primarily hinges on the sponsor’s drug development capabilities, with the quality of the drug linker being a decisive factor. Our team conducted a Phase Ia dose-escalation study of “MRG001, an anti-CD20 ADC, in patients with relapsed/refractory advanced B-cell non-Hodgkin lymphoma.” Designed according to the classic “3+3” scheme, the study enrolled a total of 21 patients with relapsed or refractory disease, including 8 with diffuse large B-cell lymphoma (DLBCL), 12 with follicular lymphoma (FL), and 1 with marginal zone lymphoma (MZL). Six dose cohorts were established among these 21 patients, with doses escalating from 0.15 mg/kg to 2.5 mg/kg. Preliminary results indicate favorable safety profiles across all dose cohorts, directly demonstrating Lepu Biopharma’s strong R&D capabilities.
Notably, the 1.8 mg/kg dose group demonstrated the optimal efficacy, with a monotherapy objective response rate (ORR) of 33% and a disease control rate (DCR) of 83%. For an antibody-drug conjugate (ADC), achieving such satisfactory efficacy in patients previously resistant to rituximab is particularly challenging.
Q: What do you think are the reasons why this study was recognized at the 2021 American Society of Hematology (ASH) Annual Meeting?
Professor Song Yuqin:Perhaps the most important reason is that CD20 has long been regarded favorably by experts in the field. In fact, nearly all patients with B-cell lymphoma express this target, making CD20 a therapeutic target with excellent prospects for research and development.
Second, although previously commonly used naked CD20 monoclonal antibodies have demonstrated considerable efficacy, some patients fail to benefit due to drug resistance. It is important to emphasize that drug resistance is not equivalent to the loss of the CD20 target. Therefore, in this context, it is remarkable that shifting the focus to the development of antibody-drug conjugates (ADCs) has achieved an objective response rate (ORR) as high as 33% along with a favorable safety profile.
Since the advent of the first CD20-targeted monoclonal antibody, anti-CD20 therapies have undergone several generations of advancement, with notable progress in hot research areas such as bispecific antibodies and CAR-T cell therapy. Currently, within the oncology sector’s antibody-drug conjugate (ADC) landscape, few candidates target CD20; most agents are directed against other targets such as CD22 and CD19. In my view, focusing on the CD20 antigen is highly appropriate for the treatment of B-cell lymphomas.
To date, only a few CD20-targeting antibody-drug conjugates (ADCs) are under investigation, with MRG001 being one of them. Relatively speaking, MRG001 has advanced rapidly in development and its clinical trials have proceeded smoothly, reflecting the diligent efforts of Lepu Biopharma’s R&D team and positioning MRG001 among the leading candidates in the fast-moving ADC landscape. Furthermore, close collaboration among researchers has created favorable conditions—timely opportunities, geographic advantages, and strong teamwork—that have contributed to the current progress. Nevertheless, there is still a long road ahead before MRG001 can be widely adopted in clinical practice.
Q: As the principal investigator of the Phase Ia study of MRG001, how do you view the future development prospects and value of MRG001 in light of the current data and the treatment landscape for non-Hodgkin lymphoma?
Professor Song Yuqin:The Phase Ia study has progressed very smoothly, a result achieved through the dedicated efforts of the entire team, including Lepu Biopharma and the investigators. Here, I would like to extend my special gratitude to all investigators participating in the study, particularly Professor Guo Ye and Professor Wang Zhao. However, this is only the beginning. The primary objective of the Phase Ia study was to evaluate drug safety, and the successful completion of the trial further demonstrates Lepu Biopharma’s R&D capabilities and the reliability of MRG001. We have selected the 1.8 mg/kg dose group as the safe and effective dose for the next stage. The ongoing dose-expansion study aims to enroll more patients, thereby allowing a broader patient population to benefit from the treatment. Subsequently, the team will conduct a Phase II registration study with the expectation of accelerating the market launch of MRG001.
Furthermore, the target population for this study comprises patients with prior resistance to rituximab. As MRG001 and rituximab both belong to the class of anti-CD20 agents, achieving superior efficacy will undoubtedly pose a significant challenge. In the future, MRG001 may be used in combination with other therapies to achieve a synergistic effect (1+1>2) in patients with CD20-positive relapsed/refractory B-cell lymphoma, which aligns with our long-term research objectives.