156P - Liver Metastases Correlate with Shortened Survival and Increased Dissociate Response in Patients Treated with T-Cell Engagers.

Background

Bispecific CD3 T cell engagers (TCEs) show promising antitumor activity in solid tumors, but resistance often develops. Resistance to immunotherapy is influenced by the tumor microenvironment (TME), including at metastatic sites. Liver metastases, for example, are linked to an immunotolerant TME and resistance. We aimed to determine if the location of metastatic sites correlates with outcomes in patients (pts) treated with TCEs.

Methods

Pts treated with a TCE for metastatic solid tumors at the Drug Development Department in Gustave Roussy were included. Clinical data were gathered during screening, and disease progression was evaluated using RECIST criteria. Target lesions (TL) progression was tracked when available. Overall survival (OS) and progression-free survival (PFS) were estimated via the Kaplan-Meier method, with multivariate analyses (MVA) conducted using a Cox regression model.

Results

The cohort included 127 pts (73 M, 57 W), with a median age of 60 years. The most common tumor types were prostate cancer (30%) and small cell lung cancer (19%). The most frequent metastatic sites were lymph nodes (69%), bones (43%), and liver (38%). MVA (on histology and metastatic sites) revealed that only liver metastases were associated with worse outcomes in both PFS (HR: 1.94, [1.19-3.17], p=0.001), with a median PFS of 58 and 89 days respectively, and OS (HR: 2.39, [1.28-4.48], p=0.007), with a median OS of 249 and 527 days respectively, independent of tumor type. Detailed data on TL progression were available for 50 pts, including 22 with at least one hepatic TL. Among these, 18 pts (79%) had at least two TLs, and 78% (14/18) exhibited a dissociated response, with 79% (11/14) showing progressive disease (PD) in the liver. Overall, 82% of pts with hepatic TL showed PD in the liver. Dissociated response tend to be more frequent in pts with liver metastases (79%) compared to those with at least two non-hepatic TL (56%) (OR : 3.7, [0.83;19.77], p=0.06).

Conclusions

In pts treated with TCEs, liver metastases are associated with poorer outcomes for both PFS and OS. Pts with liver metastases are more likely to exhibit a dissociated response to treatment, with progressive disease predominantly occurring in hepatic lesions.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N. Herbel: Financial Interests, Personal, Full or part-time Employment: Viroxis Biotech. All other authors have declared no conflicts of interest.