Data from Trastuzumab Deruxtecan with Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study
Year: 2024
Type: other
Abstract: Purpose: This multicenter phase Ib study investigated trastuzumab deruxtecan (T-DXd) plus nivolumab in patients with HER2-expressing metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC). Patients and Methods: Part 1 determined the recommended dose for expansion of T-DXd plus nivolumab. Part 2 evaluated efficacy and safety; the primary endpoint was confirmed objective response rate by independent central review. Results: In part 1, seven patients with mBC were enrolled and received T-DXd 3.2 mg/kg (four patients) or 5.4 mg/kg (three patients) plus nivolumab. The recommended dose for expansion for T-DXd was 5.4 mg/kg plus nivolumab 360 mg intravenously every 3 weeks. In part 2, 32 patients with HER2-positive mBC (cohort 1; inclusive of three administered 5.4 mg/kg in part 1), 16 with HER2-low mBC (cohort 2), 30 with HER2-high mUC (cohort 3), and four with HER2-low mUC (cohort 4) were enrolled. At data cutoff (July 22, 2021), the confirmed objective response rates (95% confidence interval) for cohorts 1 to 4 were 65.6% (46.8%−81.4%), 50.0% (24.7%−75.3%), 36.7% (19.9%−56.1%), and not assessed due to small sample size, respectively. The median treatment duration (range) with T-DXd in cohorts 1 to 4 was 8.9 (1–23) months, 6.9 (1–21) months, 3.9 (1–21) months, and not assessed, respectively; the most common treatment-emergent adverse event was nausea (55.2%, 62.5%, 73.3%, and 75.0%, respectively). Adjudicated drug-related interstitial lung disease/pneumonitis rates (cohorts 1–3) were 20.7%, 0%, and 20.0%, respectively (one grade 5 each, cohorts 1 and 3). Conclusions: T-DXd plus nivolumab demonstrated promising antitumor activity in HER2-expressing mBC or mUC and safety consistent with the known profile of T-DXd. Interstitial lung disease/pneumonitis is an important risk and requires careful monitoring and prompt intervention.
Authors: Erika Hamilton, Matthew D. Galsky, Sebastian Ochsenreither, Gianluca Del Conte, Miguel Martín, Maria José De Miguel, Evan Y. Yu, Anja Williams, Maria Gion, Antoinette R. Tan, Laila Agrawal, Annemie Rutten, Jean-Pascal Machiels, Sara Cresta, Philip R. Debruyne, Audrey Hennequin, Victor Moreno, Anna Minchom, Frances Valdes-Albini, Daniel Petrylak, Li Li, Zenta Tsuchihashi, Fumitaka Suto, Fu-Chih Cheng, Maha Kandil, Daniel Barrios, Sara Hurvitz
Language: English
Topic: HER2/EGFR in Cancer Research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4405454813