Targeting her2 with trastuzumab deruxtecan: A dose-expansion, phase i study in multiple advanced solid tumors

Junji Tsurutani, Hiroji Iwata, Ian Krop, Pasi A. Jänne, Toshihiko Doi, Shunji Takahashi, Haeseong Park, Charles Redfern, Kenji Tamura, Trisha M. Wise-Draper, Kaku Saito, Masahiro Sugihara, Jasmeet Singh, Takahiro Jikoh, Gilles Gallant, Bob T. Li

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were associated with fatal outcomes. The confirmed objective response rate (ORR) was 28.3% (17/60). Median progression-free survival (PFS) was 7.2 [95% confidence interval (CI), 4.8–11.1] months. In HER2-mutant non–small cell lung cancer (NSCLC), ORR was 72.7% (8/11), and median PFS was 11.3 (95% CI, 8.1–14.3) months. Confirmed responses were observed in six tumor types, including HER2-expressing NSCLC, colorectal cancer, salivary gland cancer, biliary tract cancer, endometrial cancer, and HER2-mutant NSCLC and breast cancer. Results suggest T-DXd holds promise for HER2-expressing/mutant solid tumors. SIGnIfICAnCE: T-DXd demonstrated promising activity in a heterogeneous patient population with heavily pretreated HER2-expressing or HER2-mutant solid tumors, especially HER2-mutant NSCLC. The safety profile was generally acceptable. Interstitial lung disease can be severe and requires prompt monitoring and intervention. Further research of T-DXd is warranted to address these unmet medical needs.

Original languageEnglish
Pages (from-to)688-701
Number of pages14
JournalCancer discovery
Volume10
Issue number5
DOIs
StatePublished - May 2020

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    Tsurutani, J., Iwata, H., Krop, I., Jänne, P. A., Doi, T., Takahashi, S., Park, H., Redfern, C., Tamura, K., Wise-Draper, T. M., Saito, K., Sugihara, M., Singh, J., Jikoh, T., Gallant, G., & Li, B. T. (2020). Targeting her2 with trastuzumab deruxtecan: A dose-expansion, phase i study in multiple advanced solid tumors. Cancer discovery, 10(5), 688-701. https://doi.org/10.1158/2159-8290.CD-19-1014