Datopotamab deruxtecan shows promising anti-tumour activity

Updated results from the phase 1 TROPION PanTumor01 study confirm promising anti-tumour activity and a manageable safety profile of the antibody-drug conjugate datopotamab deruxtecan in patients with previously treated advanced/metastatic triple-negative breast cancer (TNBC).

Effective treatment options for patients with advanced or metastatic TNBC that have relapsed or are refractory to standard treatment are limited. Over-expression of TROP2 was reported to predict poor prognosis in various solid tumours, including breast cancers [1]. Datopotamab deruxtecan is an antibody-drug conjugate consisting of a humanised anti-TROP2 IgG1 monoclonal antibody conjugated to a potent topoisomerase I inhibitor payload. Preliminary results from the multi-centre, open-label, phase 1 TROPION-PanTumor01 study (NCT03401385) demonstrated that datopotamab deruxtecan has encouraging anti-tumour activity and a manageable safety profile in patients with TNBC [2]. Dr Ian Krop (Dana-Farber Cancer Institute, MA, USA) presented updated results from the TNBC cohort [3].

A dose of datopotamab deruxtecan, 6 mg/kg intravenously, was given every 3 weeks to 42 patients. Two patients with TNBC received datopotamab deruxtecan 8 mg/kg prior to selection of 6 mg/kg for dose expansion. The median follow-up was 7.6 months. The overall response rate was 34%; the disease control rate was 77%. Median duration of response was not yet reached, with the majority of responses ongoing at data cut-off. All-cause treatment-emergent adverse events (any grade, grade ≥3) were observed in 98% and 45% of patients, respectively. Fatal adverse events were not observed. Dose reduction occurred in 18% of patients, treatment discontinuation occurred in 2% of patients. The most common adverse events (any grade) included nausea (58%), stomatitis (53%), alopecia (35%), vomiting (35%), and fatigue (33%). No cases of interstitial lung disease were observed.

“Datopotamab deruxtecan demonstrates promising anti-tumour activity with a manageable safety profile in previously treated patients with advanced/metastatic TNBC,” concluded Dr Krop. “A phase 3 trial is planned.”

1. Zeng P, et al. Sci Rep. 2016;6:33658.


2. Bardia A. ESMO Breast Cancer Congress 2021. Abstract LBA4.


3. Krop IE, et al. Datopotamab deruxtecan in advanced/metastatic HER2- breast cancer: Results from the phase 1 TROPION-PanTumor01 study. GS1-05, SABCS 2021 Virtual Meeting, 7–10 December.

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Posted on 31 January, 2022