Trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing salivary duct carcinoma: Subgroup analysis of two phase 1 studies.
Authors: Bando Hideaki , Kinoshita Ichiro , Modi Shanu , Tsurutani Junji , Bang Yung-Jue , Iwata Hiroji , Sato Yuta , Nakatani Shunsuke , Lee Caleb C. , Sugihara Masahiro , Okuda Yasuyuki , Takahashi Shunji 
Published: June 2021

6079 Background: T-DXd is an antibody-drug conjugate composed of an anti-HER2 antibody, cleavable tetrapeptide-based linker, and membrane-permeable topoisomerase I inhibitor payload. T-DXd has been approved for use in the US and Japan for both breast cancer and gastric cancer and has demonstrated safety and efficacy for additional solid tumors indications in the first-in-human (FIH) (J101; NCT02564900) and drug-drug interaction (DDI) (A104; NCT03383692) phase 1 studies. Here we present the combined subgroup analysis for salivary duct carcinoma. Methods: Patients (pts) with HER2-expressing salivary duct carcinoma after standard treatment or without any available standard treatment in both the FIH study and DDI study were included in this analysis. HER2 expression at enrollment was defined by IHC and/or amplification by ISH or NGS via local testing. A retrospective analysis of HER2 IHC and ISH of archived samples was conducted after enrollment by central laboratory per ASCO CAP guidelines. Pts with salivary duct carcinoma received T-DXd at 6.4 mg/kg and 5.4 mg/kg IV every 3 weeks in the FIH study and DDI study, respectively. RECIST version 1.1 was used for efficacy assessments by investigators. Results: Of 329 pts enrolled in both the FIH (289 pts) and DDI (40 pts) studies, a total of 17 pts with salivary duct carcinoma were pooled in this analysis: 8 pts with T-DXd at 6.4 mg/kg from FIH study and 9 pts with T-DXd at 5.4 mg/kg from DDI study. The sites of primary disease were parotid gland for 6 pts, submandibular gland for 4 pts, sublingual gland for 1 pt, and unknown for 6 pts. As for HER2 status by the central laboratory, 11 pts were IHC3+, 1 pt was IHC2+/ISH- and 5 pts had no available samples. Fourteen pts received HER2 targeted agents as a prior cancer therapy including trastuzumab. At data cutoff (FIH study: 1 Aug 2019; DDI study: 26 Sep 2018), the confirmed overall response rate was 47% (8/17) and the best overall response was PR in 8 pts and SD in 9 pts. Median duration of response and progression-free survival were 12.9 months and 14.1 months, respectively. Treatment-emergent adverse events (TEAEs) occurred in all 17 pts (grade ≥3, 64.7%); most common grade ≥ 3 TEAEs were decreased neutrophil count (8/17, 47.1%), decreased white blood cell count (6/17, 35.3%), anemia (2/17, 11.8%) and decreased platelet count (2/17, 11.8%). Three pts (3/17, 17.6%) had adjudicated drug related interstitial lung disease (Grade 1 for 2 pts and Grade 3 for 1 pt). Of these 17 pts, 7 pts (41.2%) experienced dose interruption and 3 pts (17.6%) experienced dose reduction due to TEAEs. Four pts (23.5%) discontinued treatment due to TEAEs. Conclusions: T-DXd showed promising antitumor activity in HER2-expressing salivary duct carcinoma with durable response. The safety profile was generally consistent with previous results in the other solid tumors. Clinical trial information: NCT02564900 and NCT03383692.