Abstract
BACKGROUND
DEBBRAH, ROSET-BM, TUXEDO-1, and a pooled DB-01, -02, -03 analysis indicate robust efficacy of T-DXd in patients with stable/active BMs; however, efficacy in active BMs is not yet fully established. DB-07 is a Phase 1b/2, multicenter, open-label study exploring the safety, tolerability, and antitumor activity of T-DXd alone or in combination with other anticancer agents (NCT04538742). Results are from an interim analysis of the dose-expansion phase of T-DXd monotherapy in patients with active BMs.
METHODS
Patients had locally assessed HER2+ mBC with measurable disease. No or one prior line of therapy for mBC was allowed; a ≥12-month disease-free interval from (neo)adjuvant HER2-directed therapy or chemotherapy was required. Patients had untreated BMs not requiring local therapy or progressing BMs after local therapy. Ongoing use of systemic corticosteroids (>2 mg dexamethasone daily or equivalent) for control of BMs symptoms was exclusionary. Patients received T-DXd 5.4 mg/kg intravenously every 3 weeks. Primary objectives were safety and tolerability; additional endpoints included objective response rate (ORR) and progression-free survival (PFS) per RECIST 1.1 and Response Assessment in Neuro-Oncology (RANO)-BM.
RESULTS
Thirty-five patients with active BMs were treated. As of August 1, 2023, median follow up was 11.5 months (range 5.3–24.6). The most common any-grade adverse events (AEs) were nausea (74.3%; Grade 3, 5.7%) and vomiting (45.7%; Grade 3, 2.9%); AEs Grade ≥3 occurred in 18 patients (51.4%). By RECIST 1.1, confirmed ORR was 77.1% (80% CI 65.5, 86.2), and 12-month PFS rate was 84.5% (80% CI 74.1, 91.0). By RANO-BM, confirmed ORR was 57.1% (80% CI 44.9, 68.7) and 12-month PFS rate was 74.6% (80% CI 59.4, 84.8).
CONCLUSION
The safety profile is consistent with the known profile for T-DXd, and data confirm promising efficacy in patients with active BMs. Ongoing analyses will provide more mature data.