Positive Phase III TROPION-Breast01 Trial Data Lead to BLA Submission for Datopotamab Deruxtecan for Breast Cancer


The investigational TROP2-directed antibody drug conjugate improved progression-free survival in patients with unresectable or metastatic HR-positive, HER2-negative breast cancer.

Image credit: Axel Kock | stock.adobe.com

Image credit: Axel Kock | stock.adobe.com

The FDA has accepted a Biologics License Application (BLA) from AstraZeneca and Daiichi Sankyo for datopotamab deruxtecan (Dato-DXd) based on positive data from the pivotal Phase III TROPION-Breast01 trial (NCT05104866), which enrolled adults with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer previously administered systemic therapy for unresectable or metastatic disease.1

Dato-DXd is an investigational TROP2-directed antibody drug conjugate (ADC) comprised of a humanized anti-TROP2 IgG1 monoclonal antibody that links to several topoisomerase I inhibitor payloads through tetrapeptide-based cleavable linkers. There are currently more than 20 clinical trials analyzing Dato-DXd in the treatment of multiple cancer types, including non-small cell lung cancer (NSCLC), triple-negative breast cancer, and HR-positive, HER2-negative breast cancer.

“The FDA’s acceptance of the BLA brings us closer to providing patients with previously treated HR-positive, HER2-negative breast cancer an alternative option to conventional chemotherapy earlier in the metastatic setting,” said Ken Takeshita, MD, global head, R&D, Daiichi Sankyo, in a press release. “Following our recently accepted application for advanced nonsquamous [NSCLC] in the US, along with additional regulatory reviews underway in China, the EU, Japan and other regions, we are working swiftly to bring datopotamab deruxtecan as a potential new treatment option to patients around the world.”1

In the United States, breast cancer is the second most common type of the disease among women, according to the CDC. In the United States in 2020, the latest year that incidence data are available, there were an estimated 239,612 new cases of female breast cancer reported, with 42,273 deaths from cancer.2

The global, randomized, multicenter, open-label TROPION-Breast01 trial analyzed the efficacy and safety of Dato-DXd compared with investigator’s choice of single-agent chemotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine in patients with unresectable or metastatic HR-positive, HER2-negative breast cancer whose disease progressed on, and who are not suitable for, endocrine therapy per investigator assessment and who were previously treated with at least one additional systemic therapy for unresectable or metastatic disease.

The trial’s primary endpoints are progression-free survival (PFS) as assessed by blinded independent central review and overall survival (OS), with key secondary endpoints of objective response rate (ORR), duration of response, investigator-assessed PFS, disease control rate, time to first subsequent therapy, and safety.

The results show that Dato-DXd produced a statistically significant and clinically meaningful improvement in PFS vs. investigator’s choice of chemotherapy. The novel ADC reduced the risk of disease progression or death by 37% compared with chemotherapy (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.52-0.76; p<0.001), with a median PFS of 6.9 months compared to 4.9 months in the chemotherapy cohort.3

Confirmed ORR was 36.4% in patients administered Dato-DXd vs. 22.9% in the chemotherapy cohort.3 OS data were not mature at the data cutoff date, but interim results numerically favored Dato-DXd over chemotherapy (HR 0.84; 95% CI 0.62-1.14); however, the data did not reach statistical significance at cutoff. The trial is ongoing to evaluate OS.3

“Despite marked progress in the treatment of HR-positive, HER2-negative breast cancer, most patients with advanced disease develop endocrine resistance and face the prospect of one or several lines of chemotherapy,” Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, said in the release. “If approved, Dato-DXd has the potential to provide these patients an efficacious and better tolerated alternative to conventional chemotherapy.”1


1. Datopotamab deruxtecan Biologics License Application accepted in the US for patients with previously treated metastatic HR-positive, HER2-negative breast cancer. AstraZeneca. News release. April 2, 2024. Accessed April 2, 2024. https://www.astrazeneca.com/media-centre/press-releases/2024/fda-accepts-dato-dxd-bla-for-breast-cancer.html

2. Centers for Disease Control and Prevention. Breast Cancer: Statistics. Updated June 8, 2023. Accessed September 22, 2023. Accessed April 2, 2024. https://www.cdc.gov/cancer/breast/statistics/index.htm

3. Datopotamab deruxtecan significantly extended progression-free survival vs. chemotherapy in patients with HR-positive, HER2-low or negative breast cancer in TROPION-Breast01. AstraZeneca. News release. October 23, 2023. Accessed April 2, 2024. https://www.astrazeneca.com/media-centre/press-releases/2023/datopotamab-deruxtecan-significantly-extended-progression-free-survival-vs-chemotherapy-in-tropion-breast01-phase-iii-trial.html

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