Datroway filed for TNBC in EU after data delay

Daiichi Sankyo and AstraZeneca have pressed swiftly to file for approval of their TROP2-targeting drug Datroway for triple-negative breast cancer (TNBC) in the EU, shortly after reporting positive survival data in a pivotal trial.

The application, based on the TROPION-Breast02 trial, is for the use of Datroway (dapotamab deruxtecan) as a first-line monotherapy for adults with advanced TNBC who are not candidates for PD-1/PD-L1 inhibitor therapy.

Datroway is the first drug to significantly improve overall survival (OS) versus chemotherapy in this patient population, according to the two companies, which reported the topline TROPION-Breast02 results in September after delaying the readout of the study from 2024.

It is estimated that around 70% of patients with metastatic TNBC are not eligible for this type of immunotherapy, because their tumours test negative for the PD-L1 biomarker, for example. TNBC is the most aggressive type of breast cancer, accounting for 15% of all breast cancer cases, and has one of the worst prognoses, with a median OS of just 12 to 18 months.

In the study, reported at this year's ESMO congress, Datroway achieved a median progression-free survival (PFS) of 10.8 months, compared to 5.6 months for chemo, which was a 43% improvement. OS was 21% better, coming in at a median of 23.7 months and 18.7 months, respectively.

Datroway – which is already approved for previously treated metastatic HR-positive, HER2-negative breast cancer and for previously treated advanced EGFR-mutated non-small cell lung cancer (NSCLC) – is vying with Gilead Sciences' TROP2 drug Trodelvy (sacituzumab govitecan) to provide a new standard in frontline TNBC treatment.

Gilead's bid is based on the ASCENT-03, which achieved a 38% improvement in PFS compared to chemo, but has not been able to detect an OS edge as yet. The company is also running the ASCENT-04 study of Trodelvy alongside MSD's PD-1 inhibitor Keytruda (pembrolizumab) in previously untreated, PD-L1-positive metastatic TNBC.

AZ's head of oncology and haematology R&D, Susan Galbraith, said the start of the EU review is "a meaningful step towards bringing these patients in Europe an alternative to traditional chemotherapy for the first time."

Other filings for Datroway based on the TROPION-Breast02 data are on the way, said the two companies.

Daiichi originated Datroway and has exclusive ownership of the drug in Japan, but licensed co-development rights in other markets to AZ in 2020 for $1 billion upfront, plus up to $5 billion in regulatory and sales milestones. AZ has previously pinned a $5 billion peak sales target on the ADC.