The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting took place in Chicago, USA, from May 31 to June 4. The ASCO Annual Meeting gathers oncology experts, doctors, and researchers from around the world to share the latest research findings, discuss cutting-edge diagnostic and therapeutic techniques, and advance the field of oncology. A study by Professor Jianxiang Wang and Professor Ying Wang's team from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, was selected for an oral presentation (Abstract 6505) at the conference. The study explores the therapeutic application of the CD3×CD19 bispecific antibody CN201 in relapsed/refractory adult acute B-cell lymphoblastic leukemia (R/R B-ALL), showing promising treatment prospects. "Oncology Frontier - Hematology Frontier" invited Professor Ying Wang for an interview to discuss this study and the treatment of R/R B-ALL.Oncology Frontier – Hematology Frontier: At this ASCO meeting, your team’s study on CN201 for R/R B-ALL was selected for an oral presentation. Could you briefly introduce this study?
Professor Ying Wang: CN201 is a novel CD3×CD19 bispecific antibody that has undergone structural optimization, including the addition of an Fc segment and modifications to the CD3 end to regulate its affinity and reduce cytokine release syndrome (CRS). At this ASCO meeting, we reported the results of a phase I study on CN201 for treating adult R/R B-ALL. So far, nine dose-escalation groups have been tested, showing excellent efficacy and determining the recommended phase II dose (RP2D).
Oncology Frontier – Hematology Frontier: Could you elaborate on the efficacy and advantages of CN201 in treating R/R B-ALL?
Professor Ying Wang: This study, led by Professor Jianxiang Wang, involved nine centers nationwide enrolling adult R/R ALL patients. In the era of traditional chemotherapy, the prognosis for adult acute lymphoblastic leukemia patients who relapsed or were refractory was very poor. With the emergence of immunotherapies, treatment options for R/R B-ALL have significantly expanded, including blinatumomab, the CD22-targeted antibody-drug conjugate (ADC) inotuzumab ozogamicin, and the Chinese-developed anti-CD19 CAR-T product CNCT19. Despite the various treatment options, unmet needs remain in R/R B-ALL. Blinatumomab, another CD3×CD19 bispecific antibody, has shown good efficacy and accessibility in treating R/R B-ALL, but its 24-hour continuous intravenous infusion for 28 days is not very convenient. CN201, also a CD3×CD19 bispecific antibody, has an optimized structure (including an Fc segment) and requires only weekly infusions of 2-3 hours, significantly improving treatment convenience. Additionally, phase I clinical trial data show that at a certain dose level, CN201 achieved an overall response rate (ORR) of over 70%, with more than 90% of responding patients achieving MRD negativity. In terms of safety, the overall incidence of CRS was below 30%, mostly grade 1 or 2, with a 3.9% incidence of grade 3 CRS and no grade 4 CRS. Among the 51 enrolled adult patients, no cases of ICANS were observed, indicating good overall safety. Therefore, we are very confident about the phase II clinical trial of CN201.
Oncology Frontier – Hematology Frontier: What do you see as the future research directions for R/R B-ALL, and what is your outlook on the application of CN201?
Professor Ying Wang: The research direction for R/R B-ALL treatment remains consistent: improving efficacy, reducing treatment-related toxicity, and enhancing convenience. Regarding CN201, based on the phase I clinical trial results, the overall response rate can exceed 70% at certain dose levels, making its future efficacy in R/R B-ALL highly promising. Additionally, CN201’s safety profile is reliable, with manageable CRS incidence and severity lower than that seen with CAR-T therapies. No neurotoxicity events have been observed among the 51 enrolled adult patients. The weekly intravenous dosing greatly enhances treatment convenience. We hope that further clinical trials will validate these findings, leading to CN201’s approval in China, thereby benefiting Chinese patients with R/R B-ALL.
