A phase I study presented during San Antonio Breast Cancer Symposium shows that the monoclonal antibody-drug conjugate anti-TROP2 datopotamab deruxtecan displays a durable tumor response and disease control in patients with relapsed/refractory advanced or metastatic triple-negative breast cancer, progressing after standard treatments.
The results come from patients with triple negative breast cancer enrolled for TROPION-PanTumor01 trial in the United States and in Japan, treated with datopotamab deruxtecan intravenously every three weeks at two different dosages, the lowest (6mg / kg) selected following clinical results and exposure-response analyses for safety and efficacy from the phase 3 clinical trials TROPION-Lung01 and TROPION-Breast01. The primary endpoints of the trial were safety and tolerability; secondary endpoints included efficacy, pharmacokinetics, and anti-drug antibodies; median number of prior therapies in the metastatic setting was 3 and 30% of patients had received Topo I inhibitor-based antibody-drug conjugates. Data show that overall response rate was 34% at the median follow-up of 7.6 months, with 32% of patients having a complete or partial response; 39% of the patients had a stable disease, 18% a disease progression. Overall, the disease control rate was 77%; in a median follow-up of 8.8 months in patients with triple-negative breast cancer who did not receive prior treatment with a Topo I inhibitor-based antibody-drug conjugated, the overall response rate was 52%.
«Since 30% of patients on this study had a prior Topo I inhibitor-based antibody-drug conjugate therapy and that is the same class of payload as datopotamab deruxtecan, there is a possibility of cross resistance», Ian E. Krop of the Dana-Farber Cancer Institute explained in a presentation during the conference. «Therefore, we did want to look at specifically the subset of patients who had not had 1 of these prior therapies». Datumpotamab deruxtecan is also being tested in patients with ER + / HER2- breast cancer and a phase III trial for patients with metastatic triple negative breast cancer is being planned. «Until a few years ago we had no targeted therapies at all, this is a good progress. There is potential room for looking at this drug both in pretreated patients, like what was seen here, as well as earlier lines of therapy», concludes Krop.
