442O - A phase I clinical trial of intrathecal injection of allogeneic CAR-γδT cells targeting B7H3 for the treatment of patients with recurrent glioblastoma

Background

This is the first-in-human clinical trial study on allogeneic B7H3-targeting CAR-γδT cells (QH104) for patients with recurrent glioblastoma (rGBM). The primary objective of the study is to evaluate the safety and tolerability of intrathecal infusion of QH104 in patients with B7H3-positive rGBM, and the secondary objective is to assess the preliminary efficacy and the pharmacokinetic characteristics of the infused cell in CSF.

Methods

In a single-arm, single-center phase I dose-escalation clinical trial, adult patients with B7H3-positive rGBM who had previously received standard treatment were recruited. Eligibility criteria required a KPS score of ≥60 and an expected survival of ≥3 months. Subjects received intrathecal injections of QH104, with dose escalation following the “3+3” method (1/3/10×10⁷ CAR+ cells), administered once a month. The safety, tolerability, and preliminary efficacy of multiple intrathecal reinfusions of QH104 cells were evaluated. (NCT06018363).

Results

As of March 30, 2024, a total of 7 patients with high-grade rGBM (2 females and 5 males, median age 60 years, age range 31-66 years) received more than one intrathecal infusion of QH104. The median observation time was 6.5 months, ranging from 3-10 months. Subjects tolerated the treatment well, with no dose-limiting toxicity (DLT). The most common adverse events were fever and headache, accompanied by an increase in IL-6 and IFN-γ in the CSF, with no grade 3 or higher severe CRS or ICANS occurring, and no GvHD observed. Among all 7 subjects, the objective response rate (ORR) was 42.9% (3/7), and the disease control rate (DCR) was 100% (7/7). QH104 showed excellent persistence, with infused cells still detectable in the CSF by FACS and qPCR 30 days after administration. Preliminary stratified analysis found that clinical efficacy was positively correlated with the B7H3 expression level.

Conclusions

In summary, these data suggest that QH104 exhibits good safety and holds excellent clinical potential for treating patients with B7H3-positive rGBM.

Clinical trial identification

NCT06018363.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Unicet Biotech.

Disclosure

All authors have declared no conflicts of interest.