Triple Negative Breast Cancer Metastatic Clinical Trial
Official title:
Restoring Sensitivity To Immunotherapy In Advanced Triple Negative Breast Cancer Exploiting Ceralasertib Priming Followed By Combined Durvalumab/Nab-Paclitaxel: The ATRiBRAVE Trial
This study will evaluate the efficacy and safety of ceralasertib followed by durvalumab plus nab-paclitaxel in 37 patients with TNBC, whose tumor relapsed following treatment with curative intent for early disease, which must have included immunotherapy and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both).
ATRiBRAVE is a phase II, single-arm, open-label trial conducted in 37 TNBC patients with unresectable locally advanced or metastatic TNBC whose tumor relapsed following previous curative intent treatment for early disease, which must have included ICIs and chemotherapy as part of the radical locoregional therapy (either adjuvant, neoadjuvant or both). Enrolled patients will be treated with Ceralasertib, Durvalumab and Nab-paclitaxel. Given that the safety profile of the triple combination has not been evaluated in advanced TNBC patients so far, a safety run-in phase will be carried out using a 3+3 de-escalating schema down to -2 ceralasertib dose level. Once the definitive dose for ceralasertib is established, treatment will be continued until progression or unacceptable toxicity, which ever come first. Tumor assessments will be performed every 8 weeks (± 1 week) for the first 12 months after treatment initiation and every 12 weeks (± 1 week) thereafter until PD per RECIST v1.1 or death, withdrawal of consent, or study termination by the Sponsor, whichever occurs first. Tumor assessments will be performed according to the pre-specified schedule regardless of treatment delays. Blood (mandatory) and tumor (optional) samples will be collected at specific timepoints in order to conduct exploratory biomarker assessments, investigating mechanism of the study treatments within the tumor microenvironment, possible resistance mechanisms, potential predictive and prognostic markers. ;