Sustained Remission and Decreased Severity of CAR T-Cell Related Adverse Events: A Pivotal Study Report of CNCT19 (inaticabtagene Autoleucel) Treatment in Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-Cell ALL) in China

CNCT19 (inaticabtagene autoleucel) is an autologous CD19-specific chimeric antigen receptor (CAR) T-cell product. The patent protected CAR structure of CNCT19 contains a unique CD19 scFv, HI19a, which is different from commonly used FMC63. Together with using 4-1BB co-stimulatory domain in the CAR structure, CNCT19 is expected to reduce the severity of treatment-associated cytokine release syndrome (CRS) and neurologic toxicities (NT) while maintaining a stronger and longer durable anti-tumor effect.CNCT19 has been granted Breakthrough Therapy Designation by China National Medical Products Administration and Orphan Drug Designation by the U.S. FDA for the treatment of ALL.The trial of CNCT19 in adult Chinese patients with R/R B-cell ALL (NCT04684147) is a single-arm, open-label pivotal study conducted at 10 centers in China. The primary endpoint was the overall complete response rate (OCR) of complete response (CR) and CR with incomplete hematological recovery (CRi) within 3 months and at the end of Month 3 after CNCT19 infusion by central assessment.All 39 patients diagnosed with B-cell ALL were refractory and relapsed to multiple lines of prior therapy. Among the 39 patients 32 (82.1%) had reached MRD-negative OCR within 3 months after CNCT19 infusion, The median duration of response and OS have not been reached. 25 patients (64.1%) remained on CR (51.3%) or CRi (12.8%). at the end of Month 3 after CNCT19 infusion These patients had sustained long-term remission regardless of whether subsequent allo-HSCT treatment was done or not. The most common CNCT19-related adverse events (AEs) were CRS and NT and there were 4 cases of Grade ≥ 3 CRS (n=4, 10.3%) and 3 cases of Grade ≥ 3 NT (n=3, 7.7%). Following CNCT19 infusion, all the patients recovered. No death cases were reported due to CRS or NT.CNCT19 CAR-T cell therapy achieved a high rate of MRD-negative complete remission in adult patients with R/R B-cell ALL. Thus, with its distinct CAR structure containing a unique CD19 scFv (HI19a), CNCT19 provides effective treatment with potential long-term clinical benefits for adult patients with R/R B-cell ALL.