Introduction: Acute lymphoblastic leukemia (ALL) is one of the most common malignant tumors in children and a leading cause of mortality in children and adolescents. The chimeric antigen receptor (CAR-T) cell therapy has revolutionized the treatment of relapsed/refractory (R/R) B-cell ALL, with the first FDA-approved product, Kymriah (tisagenlecleucel) developed by Novartis, significantly improving remission rates and survival times.

pCAR-19B is an autologous CAR-T cell product with an optimized humanized CD19-specific single-chain variable fragment (scFv) designed to address safety concerns. pCAR-19B has been granted “Breakthrough Therapy Designation” by the China National Medical Products Administration for treating B-ALL. This report presents the efficacy and safety outcomes of pCAR-19B in a pivotal clinical trial involving Chinese pediatric and young adult patients with R/R B-cell ALL.

Methods: This phase 2 trial (NCT05334823) was a single-arm, open-label, multicenter study. Patients aged ≥ 3 and ≤ 21 years at screening with confirmed CD19+ R/R B-ALL were included. The primary endpoint was the overall remission rate (ORR), defined as complete remission (CR) plus CR with incomplete blood recovery (CRi) within 3 months post-infusion.

Results: As of April 18th, 2024, 89 patients had been enrolled and underwent leukapheresis, with 64 patients receiving pCAR-19B infusion. There were no cases of manufacturing failure. Among the infused patients, 6.25%(4/64）were refractory and 93.75%(60/64) had relapsed to multiple lines of prior therapy or allogeneic stem cell transplant. The median age was 11 years (range 3-21), and 56.25% (36/64) were male. Additionally, 75% (48/64) of the patients carried at least one high-risk gene. The median bone marrow (BM) blast burden at baseline was 58.3% (range 5%-98%) with a heavy BM blast burden (≥50%) observed in 56.25% of the patients.

At a median follow-up of 211 days (range 35-750), the best ORR was 90.63% (58/64), with 78.13% of patients (50/64) achieving CR and 12.5% of patients (8/64) achieving CRi, surpassing the efficacy of the commercial anti-CD19 CAR-T therapy products reported in R/R B-ALL. 98.27% (57/58) of patients with ORR achieved negative minimal residual disease (MRD)-negative remission. The ORR at 3 months was 76.56% (49/64). The median duration of response (DOR) was 10.61 months (95% confidence interval 7.66-20.96). The median overall survival (OS) was 23.92 months (95% confidence interval 9.86-NR).

Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 98.44% and 50% of patients, respectively. Grade ≥3 CRS and ICANS were observed in 29.69% and 39.06% of patients, respectively. The median duration of Grade ≥3 CRS and ICANS was 4 days and 3 days, respectively. There were no deaths attributed to CRS or ICANS.

Conclusions: Despite a heavy burden of BM blasts and a high risk of genetic variations, pCAR-19B demonstrated high remission rates, achieved a high rate of MRD-negative remission, durable responses, and a tolerable safety profile. This study represents the first pivotal clinical trial of childhood B-ALL in an Asian population, offering a new treatment option for Chinese pediatric and young adult patients with R/R B-ALL.

Disclosures

Zhang:Chongqing Precision Biotech Co., Ltd., Chongqing, China: Current Employment. Yang:Chongqing Precision Biotech Co., Ltd., Chongqing, China: Current Employment. Huang:Chongqing Precision Biotech Co., Ltd., Chongqing, China: Current Employment. He:Chongqing Precision Biotech Co., Ltd., Chongqing, China: Current Employment. Qian:Chongqing Precision Biotech Co., Ltd., Chongqing, China: Current Employment.

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2024
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