AstraZeneca, Daiichi hit first goal in pivotal breast cancer ADC trial, teeing up filings to challenge Gilead

AstraZeneca and Daiichi Sankyo are coming for Gilead Sciences' breast cancer business. The partners plan to file for approval of datopotamab deruxtecan (Dato-DXd) after linking their antibody-drug conjugate (ADC) to improved outcomes, although the immature overall survival (OS) data leave a key question unanswered. 

Dato-DXd is the next ADC from the production line that delivered Enhertu. In July, the partners shared phase 3 data on the TROP2-directed candidate in non-small cell lung cancer (NSCLC), spooking investors with a top-line data set that included fatal adverse events and immature OS data. Now, AstraZeneca and Daiichi are back with top-line data in breast cancer, a setting in which Gilead’s rival Trodelvy is approved.

The data come from a clinical trial that enrolled more than 700 patients with inoperable or metastatic HR-positive, HER2-low or negative breast cancer who were previously failed by endocrine therapy and one or more systemic therapies. Participants received Dato-DXd or single-agent chemotherapy.

Dato-DXd improved progression-free survival compared to chemotherapy, causing the study to hit one of its dual primary endpoints. The other primary endpoint is looking at OS. And, on that point, AstraZeneca and Daiichi failed to present a fully united front in their press releases. 

The statements put out by the companies are very similar, with changes largely limited to the reordering of paragraphs. But the releases differ on one point with the potential to shape perceptions of Dato-DXd’s prospects and move share prices. Both releases state the OS data are immature, but only AstraZeneca added the sweetener that “a trend in improvement” has been observed.  

With the partners yet to share the numbers, investors and analysts will scrutinize the wording for hints of how well Dato-DXd is performing, as was shown when the lack of the descriptor “clinically meaningful” in the earlier NSCLC statement raised concerns. The question of whether Dato-DXd is on track to hit the OS endpoint is important because Gilead has linked Trodelvy to improved overall survival.

More details will emerge when AstraZeneca and Daiichi share data at an upcoming medical meeting. Preparations for the meeting are advancing as the companies ready submissions for approval of the ADC in breast cancer. AstraZeneca and Daiichi continue to study Dato-DXd in two other phase 3 breast cancer trials that could support the use of the ADC in a broader patient population. 

Shares in AstraZeneca rose 2.7% in early trading in London after the release of the top-line results.