Datopotamab Deruxtecan Shows Promise in Heavily Pretreated Triple-Negative Breast Cancer


The TROP2-directed antibody-drug conjugate datopotamab deruxtecan induced responses and an acceptable safety profile in a cohort of patients with triple-negative breast cancer treated on a phase 1 trial.

Patients with relapsed/refractory metastatic triple-negative breast cancer (TNBC) who were treated with datopotamab deruxtecan (Dato-DXd) demonstrated antitumor activity and tolerability of the agent, according to results of a phase 1 trial that was presented at the European Society for Medical Oncology Breast Cancer Virtual Congress 2021.1,2

The TROPION-PanTumor01 study (NCT03401385) is a first-in-human enrolling patients with TNBC as well as non–small cell lung cancer who have relapsed on standard therapies or for whom no standard treatment is available. Preliminary results from the TNBC group were reported at the meeting.

“There are currently limited treatment options for patients with previously treated metastatic triple negative breast cancer, historically a very difficult-to-treat subtype of breast cancer,” Aditya Bardia, MD, MPH, of Mass General Cancer Center and Harvard Medical School, said in a press release. “These initial safety and efficacy results of datopotamab deruxtecan in patients with triple-negative breast cancer are encouraging and warrant further development for patients with breast cancer.”

Dato-DXd is an antibody-drug conjugate (ADC) directed at TROP2 being developed by Daiichi Sankyo and AstraZeneca. It is made up of a humanized anto-TROP2 IgG1 antibody conjugated to DXd, a potent topoisomerase I inhibitor payload.

In patients evaluable for response, the objective response rate was 43% across both doses of 6 mg/kg (n = 19) and 8 mg/kg (n = 2). Five complete or partial responses were confirmed, and 4 additional responses were awaiting confirmation at the data cut-off of January 8, 2021. There was a disease control rate of 95% in this group. Only 1 patient (5%) had progressive disease on the therapy.

The safety profile of Dato-DXd in TNBC was consistent with that reported in the NSCLC cohort, results of which were made available at the 2020 World Conference on Lung Cancer.3 No treatment discontinuations were the result of therapy adverse events (AEs). Six patients had dose reductions due to treatment-related AEs, including stomatitis (13%) and mucosal inflammation (8%).

Treatment-emergent AEs (TEAEs) occurred in 33%, with grade 3 effects including stomatitis (13%), fatigue (4%), and anemia (4%). Notably, there were not grade 3 or higher events of neutropenia or diarrhea reported. The most common all-grade TEAEs to occur in 25% of patients or more were stomatitis, nausea, fatigue, vomiting, and alopecia. No cases of interstitial lung disease determined to be related to therapy were reported.

“These preliminary results provide proof-of-concept that targeting TROP2 with datopotamab deruxtecan may be an effective treatment strategy for patients with previously treated metastatic triple negative breast cancer,” Gilles Gallant, BPharm, PhD, FOPQ, senior vice president and Global Head of Oncology Development and Oncology R&D at Daiichi Sankyo, said in the press release. “We are encouraged by the early tumor responses and disease control seen in these patients and we will continue to explore the potential of datopotamab deruxtecan in several types of breast cancer, including triple-negative breast cancer.”

Patients in the TNBC cohort had a median of 4 prior lines of therapy (range, 1-9) which included therapies in the adjuvant, neoadjuvant, and metastatic settings. Most patients (88%) had received at least 2 prior therapy lines, including a taxane (83%); platinum-based chemotherapy (50%); immunotherapy (33%); sacituzumab govitecan (Trodelvy), another TROP2-directed ADC; and a PARP inhibitor (4%). At data cut-off, 75% of patients remained on therapy.

“Triple-negative breast cancer is known to be particularly aggressive and fast growing, and after treatment the risk of recurrence is faster and higher than in any other breast cancer subgroup,” Cristian Massacesi, senior vice president and Head of Late Stage Development Oncology R&D at AstraZeneca, said in the press release. “The preliminary results for datopotamab deruxtecan in this cohort of pretreated patients are encouraging for this high-potential targeted ADC.”


1. Datopotamab Deruxtecan Late-Breaking Data at ESMO Breast Shows Promising Preliminary Response and Disease Control in Patients with Metastatic Triple Negative Breast Cancer. News release. Daiichi Sankyo Compant, Limited and AstraZeneca. May 8, 2021. Accessed May 10, 2021. https://bwnews.pr/3vVt3rO

2. Bardia A. Datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate (ADC), for triple-negative breast cancer (TNBC): Preliminary results from an ongoing phase 1 trial. Ann Oncol. 2021;32(suppl2):S60-S78. Abstract LBA4. doi:10.1016/annonc/annonc508

3. Datopotamab deruxtecan and Enhertu show promising early clinical activity in patients with advanced non-small cell lung cancer. News release. AstraZeneca. January 29, 2021. Accessed May 10, 2021. https://bit.ly/3he6gU4

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