657P - Prospective validation of the T cell engager (TCE) score in patients treated with bispecific CD3 TCE antibodies in phase I clinical trials

Background

T cell engagers (TCE) have been a breakthrough in pts care for multiple malignancies, and the number of phase I clinical trials testing TCE is exponential. The TCE score, based on lactate dehydrogenase (LDH) (LDH > 250 U/l : +1) and C reactive protein (CRP) (CRP > 10g/l : +1) levels, that was developed on a setting cohort (presented at ASCO annual meeting in 2023, Noé Herbel et al., JCO 41, 2573-2573(2023)), was shown to be prognostic for both overall survival (OS) and progression free survival (PFS), as pts with a high score (1-2) had a shorter OS and PFS, with a median PFS of less than two months : thus not presenting a sufficient clinical benefit from the treatment. To confirm the results obtained on the setting cohort, we aimed to prospectively confirm the prognostic ability of the TCE score on a validation cohort.

Methods

Every pts treated with a CD3 TCE in a phase I CT at the drug development department (DITEP) at Gustave Roussy which were not part of the setting cohort, with at least a two months follow up, were included in the validation cohort. Biological and clinical data were prospectively collected to calculate the TCE score, the OS and the PFS. Biological data were collected during the screening period. Estimation of OS and PFS was made using Kaplan-Meir method and comparison using log-rank test. Cox regression model was used in univariate analysis. Predictive power of the TCE score was analyzed using Harrell's C index.

Results

A total of 70 pts treated with CD3 TCE were included in the validation cohort. Median age was 60 years old. The most represented tumor type was ovarian adenocarcinoma (21%). Kaplan-Meier, log-rank test and cox regression model showed that pts with a low score had a longer PFS (HR : 0.42, 95%CI = 0.23 - 0.78, p = 0.005), with a median PFS of 1.8 months (m) for high-risk pts and 5.5 m for low-risk pts. It was also showed that low risk pts have a longer OS (HR : 0.41, 95%CI = 0.18 - 0.93, p = 0.03, with a median 8.7 m for high-risk pts and 12.4 m for low-risk pts. TCE score’s Harrell’s C index for PFS was 0.61 and 0.62 for OS.

Conclusions

The TCE score was developed on a setting cohort to be prognostic for OS and PFS in pts treated with bispecific TCE in phase I CT. We prospectively validated this score on an independent validation cohort.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.