Daiichi and AZ pull Dato-DXd filing in Europe too

AstraZeneca and Daiichi Sankyo confirmed today that they have decided to voluntarily withdraw their EU marketing application for datopotamab deruxtecan (Dato-DXd) in lung cancer, based on regulator feedback.

The move comes shortly after the two partners pulled their marketing application for the same indication – the treatment of adult patients with locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who have received prior systemic therapy – in the US.

In a statement, they said the EU decision came after discussions with the EMA's human medicines committee, the CHMP, about the data from the TROPION-Lung01 study used to support the filing of the TROP2-targeting antibody-drug conjugate (ADC).

They added however that they will "continue to work to bring datopotamab deruxtecan to patients with lung cancer in the EU who can benefit." As in the US, Dato-DXd remains under review for he treatment of HR-positive, HER2-negative metastatic breast cancer based on the TROPION-Breast01 study.

In TROPION-Lung01, Dato-DXd showed a statistically significant improvement in progression-free survival (PFS) in NSCLC patients treated with at least one prior therapy when compared with docetaxel, a standard form of chemotherapy for this patient group, coming in at 5.6 months and 3.7 months, respectively.

It wasn't a compelling result, however, with most of the benefit coming in non-squamous NSCLC patients with little impact in the squamous group, prompting Daiichi Sankyo and AZ to go after a narrower indication in the non-squamous population only.

Added to that, a trend to an improvement in overall survival (OS) in the non-squamous cohort failed to reach statistical significance with further follow-up.

AZ and Daiichi Sankyo are working to get the programme in lung cancer back on track, with seven pivotal trials on the go across various lung cancer settings.

In the US, the two companies have opted to refile Dato-DXd based on the phase 2 TROPION-Lung05 trial in a heavily pretreated group of EGFR-mutated NSCLC patients, which would be a much smaller patient population for the drug. It's not clear yet if they will adopt the same go-to-market strategy in Europe.

Preliminary results from TROPION-Lung05 reported at the main ESMO congress last year revealed an overall response rate (ORR) of 35.8% and a disease control rate (DCR) of 78.8%, with a median duration of response of seven months.

AZ licensed rights to Dato-DXd from Daiichi Sankyo in July 2020 for $1 billion upfront, plus up to $5 billion in regulatory and sales milestones.