Despite unfavorable Phase III trial results, AstraZeneca and Daiichi Sankyo have secured US Food and Drug Administration (FDA) approval for Datroway (datopotamab deruxtecan or Dato-DXd) as a treatment for a subset of unresectable or metastatic breast cancer patients.
The regulatory agency has approved the therapy as a treatment for hormone receptor (HR)-positive, HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer patients who have received prior endocrine-based therapy and chemotherapy for unresectable or metastatic disease.
The approval was based on the data from the Phase III TROPION-Breast01 (NCT05104866). Although Datroway was able to significantly reduce disease progression. The overall survival (OS) rate in the Datroway group was comparable to the Investigator’s choice of a standard-of-care single-agent chemotherapy arm, 18.6 months versus 18.3 months respectively.
The Datroway nod marks the second US approval of the antibody-drug conjugate (ADC) developed as part of AstraZeneca and Daiichi Sankyo partnership and follows the successful rollout of Enhertu (trastuzumab deruxtecan). The HER2 ADC generated $1.4 billion in sales in the first nine months of 2024, as per AstraZeneca’s financials.
Datroway is a tumor-associated calcium signal transducer 2 (TROP-2)-directed ADC, comprising of humanised anti-TROP2 IgG1 monoclonal antibody attached to several topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. AstraZeneca acquired the worldwide rights to the therapy excluding Japan, where Daiichi Sankyo retains these rights, in 2020.
The ADC is approved in the specific breast cancer indication in Japan, with AstraZeneca noting that “submissions for Datroway in breast cancer are under review in the EU, China, and other regions”. The British pharmaceutical giant boasts that Datroway approval marks the eighth new medicine of the 20 AstraZeneca promised to deliver by 2030. Adding that the therapy will be available by prescription in the US in about two weeks.
Phase III trial results
The open-label Phase III TROPION-Breast01 enrolled 732 patients who received either Datroway or the Investigator’s choice of standard-of-care single-agent chemotherapy (active control). The trial’s co-primary endpoints were progression-free survival (PFS) and OS. The median PFS of the Datroway arm was 6.9 months, compared to 4.9 months seen in the active control group.
Median OS was comparable across both arms, 18.6 months versus 18.3 months for the Datroway and active control groups, respectively. Other efficacy outcomes included objective response rate (ORR) and duration of response (DOR). The median ORR was 36% and 23% and the median DOR was 6.7 months and 5.7 months in the Datroway and control arms, respectively.
AstraZeneca and Daiichi Sankyo are also evaluating Datroway in lung cancer patients. In November 2024, submitted a new Biologics License Application (BLA) for accelerated approval in the US for Datroway as a treatment of a subset of non-small cell lung cancer (NSCLC). The news came a few months after the companies submitted a BLA for the board approval of the therapy in the non-squamous NSCLC indication.
It was a dual approval day for AstraZeneca as the company also received FDA approval for Bruton’s tyrosine kinase (BTK) inhibitor, Calquence (acalabrutinib) as a first-line combination therapy for treating patients with previously untreated mantle cell lymphoma (MCL).
