Anti-disialoganglioside (GD2)-targeted third-generation chimeric antigen receptor T cells (GD2-CART01) have shown promising efficacy in children with high-risk metastatic, relapsed, and refractory neuroblastoma.

A phase 1/2 trial led by Franco Locatelli, MD, at the Department of Hematology/Oncology, Cell and Gene Therapy, IRCCS, Bambino Gesù Hospital in Rome, Italy, was published in Nature Medicine.

Preliminary data published in 2023 in The New England Journal of Medicine included 27 patients and showed a response rate exceeding 60%, with a 3-year event-free survival rate of 36%.

The updated study expanded the cohort to 54 children and extended the follow-up period, reinforcing the potential of this treatment to offer durable remission for this aggressive childhood cancer.

These findings highlight GD2-CART01 as a significant advancement in immunotherapy, offering new hope for children with limited treatment options.

Of these children, 35 were treated within the clinical trial, and 19 were treated under a hospital exemption program using the same eligibility criteria.

The overall response rate (ORR) was 66%. Complete remission was achieved in 37%, 34%, and 40% of patients at 6 weeks, 3 months, and 6 months, respectively. In the trial cohort, the 5-year overall survival (OS) reached 42.7% after a median follow-up of 4.2 years.

Children with a lower disease burden experienced the most favourable outcomes. In this group, the ORR increased to 77%, with a 5-year OS of 68% and an event-free survival of 53%.

The best results were observed when the cells were collected at the time of diagnosis rather than after multiple lines of treatment. Children treated after one or two prior treatments had a 5-year survival rate of 89% compared with 43% after three or more treatments.

The safety profile was consistent with that of the CAR T-cell treatment. Cytokine release syndrome was reported in approximately 80% of patients, mostly mild to moderate.

Neurotoxicity occurred in 10 children, including four grade 3 cases.

In these children, activation of the iC9 suicide gene when paired with the drug rimiducid enables rapid reversal of neurotoxicity symptoms.

Early and late haematologic toxicities were common and sometimes severe, in line with the outcomes observed in patients with extensive prior treatment.

Importantly, no new long-term safety concerns were observed. Although one case of a secondary central nervous system tumour has been reported, it was not directly linked to the treatment.

The investigators cautioned that the small cohort limits generalisability, even accounting for the heterogeneity of high-risk or relapsed/refractory neuroblastoma.

“Compared to the interim analysis from 2023, the data published today confirm and even improve the results: We have demonstrated that, when administered under the appropriate conditions, GD2 CAR T-cell therapy offers children affected by this serious disease long-lasting recovery prospects,” Locatelli said in a press release.

An international, multicentre phase 2 trial is underway to validate and expand these findings.

Locatelli reported having no relevant financial relationships. This study was supported by AIRC Foundation for Cancer Research, Italy; Italian Ministry of Health; the Ministry of University and Research; and the Ministry of Enterprises and Made in Italy.

This story was translated from Univadis Italy.