Paolo Tarantino, MD, of Dana-Farber Cancer Institute, presented new findings from the DATO-Base study examining treatment with the ADC Dato-DXd for women with leptomeningeal disease. Breast cancer is the most common cancer linked to this rare but serious condition.
We know that patients with brain metastasis from breast cancer face a particularly poor prognosis, and probably the most aggressive condition is patients with lepto meningeal spread of disease. These patients are usually excluded from clinical trials because of this poor prognosis, and so we have very little data on the activity of drugs in this population. To fill this gap, we designed database. There is a phase 2 trial, multi-cohort for patients with either active brain metastasis or lepto meningeal disease. All patients on the trial are treated with a novel ADC targeting TRP 2 called daropoamabdoxican, and this drug is approved for metastatic breast cancer, but it was not tested yet for patients with leptomningeal disease. We enrolled 10 patients in the database. And what we observed is that there was a 30% lear intracranial response rate with Dao DXT, a median PFS of about 4 months, and a median overall survival of approximately 5 months. However, overall survival reached up to 13 months among patients that had not received prior antibody drug conjugates, which makes maybe the population more sensitive to the rapotamidruxican. We also Looked at neurological symptoms and the majority of patients that had neurological symptoms at baseline developed improvement of neurological symptoms. We looked at toxicities which were expected based on the profile of Da DXT, and finally we evaluated HER2 and TROP 2 expression with a novel assay called high sensitivity HER2 and high sensitivity THROP 2, and most of the benefit with Dao-DXD was observed among patients that had the lowest HER2. To expression suggesting that in the future this assay, if validated, could drive decision making when more than one ADC is available. Now the next efforts will be to fully enroll the cohorts A and code B. There are patients with hormone receptor positive or triple negative active brain metastasis, but we really look forward to presenting this data on leptto meningeal disease at San Antonio in Texas.
