Inaticabtagene Autoleucel (CNCT19 Injection) is the first core product candidate of Juventas Cell Therapy, it is also the first CD19-directde CAR-T product with Chinese independent intellectual property rights. CD19 scFv (HI19a) structure and CMC technique. It has obtained three IND approval from the National Medical Products Administration (NMPA), for the treatment of adult relapsed and refractory acute lymphoblastic leukemia, relapsed and refractory aggressive B-cell non-Hodgkin lymphoma, and pediatric and adolescent B-cell acute lymphoblastic leukemia. In addition, it was granted Breakthrough Therapy Designation by Center for Drug Evaluation, National Medical Products Administration (CDE, NMPA) and Orphan Drug Designation (ODD) by the U.S. FDA. Nov 2023, China's NMPA has formally approved its New Drug Application (NDA) for Inaticabtagene Autoleucel for the treatment of adult relapsed and refractory B-cell acute lymphoblastic leukemia (r/r B-ALL).

Adult acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the disruption of lymphoid cell differentiation at the stem/progenitor cell stage. This disease manifests itself through the infiltration of leukemic cells into the bone marrow, peripheral blood, and extramedullary tissues, constituting a prevalent subtype, representing 20% to 30% of adult acute leukemia cases ^[1,2]. Distinctly classified based on lineage, B-ALL and T-ALL are the primary subtypes, with the former comprising the majority in the Chinese adult population, accounting for 66% of all cases ^[3].

Despite advancements in chemotherapy, nearly 50% of adult ALL patients experience relapse post-treatment, with an additional 10% failing to achieve complete remission (CR) during induction therapy ^[4]. The prognosis for patients with relapsed or refractory ALL (R/R ALL) is grim, characterized by a median overall survival ranging from 2 to 6 months and a 3-to-5-year survival rate of less than 10% ^[5]. An observational study conducted in 2018, encompassing 270 adults with Philadelphia chromosome-negative (Ph-) R/R B-ALL from 14 prominent hematology centers in China, reported that 31% of patients achieved CR or CR with partial hematological recovery (CRh) following salvage therapy with chemotherapy. The average duration of CR or CRh was a mere 2.7 months ^[6].

The management of R/R ALL poses a formidable challenge in current clinical practice, highlighting the imperative for the development of more efficacious treatment modalities ^[7].

[1]Malard F,Mohty M.Acute lymphoblastic leukaemia[J].Lancet,2020,395(10230):1146-1162.
[2]中国抗癌协会血液肿瘤专业委员会,中华医学会血液学分会白血病淋巴瘤学组.中国成人急性淋巴细胞白血病诊断与治疗指南(2021年版)[J].中华血液学杂志, 2021,42(9):705-716. 
[3]陈赛娟.全国成人白血病登记研究工作结果[Z].第19次全国实验血液学学术会议.2023.
[4]Gökbuget N,Hoelzer D.Treatment of adult acute lymphoblastic leukemia[J].Semin Hematol,2009,46(3):64-75.
[5]中国临床肿瘤学会白血病专家委员会,中国临床肿瘤学会淋巴瘤专家委员会,中华医学会血液学分会.双特异性T细胞衔接器治疗急性淋巴细胞白血病指导原则(2022年版)[J].中华血液学杂志,2022,43(06):448-455.
[6]Ma J,Liu T,Jin J,et al.An observational study of Chinese adults with relapsed/refractory philadelphia-negative acute lymphoblastic leukemia.International journal of hematologic oncology[J].Int J Hematol Oncol,2018,7(2):IJH06.
[7]王建祥.中国复发难治急性淋巴细胞白血病的治疗概况[J].中国实用内科杂志,2021,41(4):25-32.