ORCID
- Philip Debruyne: 0000-0001-5438-9697
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.
DOI Link
Publication Date
2024-12-15
Publication Title
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
30
Issue
24
Acceptance Date
2024-10-10
Deposit Date
2025-11-03
Additional Links
Recommended Citation
Hamilton, E., MD, G., Ochsenreither, S., Del, C., Martín, M., MJ, d., EY, Y., Williams, A., Gion, M., AR, T., Agrawal, L., Rutten, A., JP, M., Hurvitz, S., & Debruyne, P. (2024) 'Trastuzumab Deruxtecan With Nivolumab in HER2-Expressing Metastatic Breast or Urothelial Cancer: Analysis of the Phase Ib DS8201-A-U105 Study.', Clinical cancer research : an official journal of the American Association for Cancer Research, 30(24). Available at: 10.1158/1078-0432.ccr-24-1513
