AZ, Daiichi get FDA nod for Dato-DXd in breast cancer
AstraZeneca and Daiichi Sankyo have claimed FDA approval for a second antibody-drug conjugate (ADC) for breast cancer, hoping to build on the success of a partnership that already spawned a blockbuster drug.
The US regulator has cleared TROP2-directed ADC datopotamab deruxtecan (Dato-DXd) under the Datroway trade name as a treatment for previously treated HR+/HER2- breast cancer, a few weeks after its first world approval in Japan.
Datroway is the second ADC brought to market by AZ and Daiichi Sankyo after Enhertu (trastuzumab deruxtecan), an HER2-targeting ADC that brought in sales of more than $2.7 billion in the first nine months of 2024 – up from $1.8 billion in the same period of 2023 – from half a dozen indications across breast, lung, and gastric cancer, as well as HER2-positive solid tumours.
The FDA approval of Datroway is based on the results of the TROPION-Breast01 study, which showed that patients treated with the ADC had a median progression-free survival (PFS) of 6.9 months compared to 4.9 months for those receiving physicians' choice of chemotherapy, a 37% improvement.
"Despite considerable progress in the HR-positive, HER2-negative metastatic breast cancer treatment landscape, new therapies are still needed to tackle the frequent and complex challenge of disease progression after endocrine and initial chemotherapy," said Aditya Bardia of UCLA Health Jonsson Comprehensive Cancer Center, the principal investigator in TROPION-Breast01.
She added that Datroway's approval "marks a major therapeutic milestone and provides patients with metastatic breast cancer a new treatment alternative to conventional chemotherapy."
Only one in three patients with this type of breast cancer live more than five years following diagnosis.
Other indications
AZ and Daiichi Sankyo have aspirations to extend the uses of Datroway into other types of cancer, including locally advanced or metastatic non-small cell lung cancer (NSCLC), but were forced to pull their marketing applications for the drug as a second-line therapy for this indication in the US and EU after feedback from regulators suggested the data from their pivotal TROPION-Lung01 study was not strong enough to support approval.
It wasn't a compelling result, with a two-month improvement in PFS benefit in non-squamous NSCLC patients only, with little impact in the squamous group, prompting Daiichi Sankyo and AZ to try unsuccessfully for a narrower indication. Subsequently, a trend to an improvement in overall survival (OS) in the non-squamous patients failed to become statistically significant.
Towards the end of last year, the two partners opted to refile Datroway based on the mid-stage TROPION-Lung05 trial, which is looking at the use of the ADC in a heavily pretreated group of EGFR-mutated NSCLC patients, backed up by data from TROPION-Lung01 and TROPION-PanTumor01. Last week, the FDA granted that indication a priority review.
Meanwhile, several other studies of Datroway are ongoing as the partners chase down what AZ has predicted could be peak sales of around $5 billion for the drug.
Near-term readouts include the TROPION-Breast02 study comparing the ADC to chemotherapy in advanced triple-negative breast cancer (TNBC) who are not eligible for PD-1/PD-L1 inhibitor therapy, and the AVANZAR study of Datroway plus AZ's PD-1 inhibitor Imfinzi (durvalumab) and chemotherapy in previously untreated advanced NSCLC.
