AstraZeneca and Daiichi's HER2 ADC hits goal in pivotal trial

José Baselga
AstraZeneca Executive Vice President José Baselga (MSKCC)

AstraZeneca and Daiichi Sankyo’s HER2-targeting antibody drug conjugate (ADC) has hit the primary endpoint in a pivotal phase 2 trial, teeing the partners up to file for FDA approval in the first half of the fiscal year.

The readout comes shortly after AstraZeneca paid $1.35 billion upfront and committed to up to $5.5 billion in milestones for a stake in Daiichi’s anti-HER2 ADC [fam-] trastuzumab deruxtecan (DS-8201). 

Now, AstraZeneca and Daiichi have revealed that a phase 2 trial of the ADC met its primary objective response rate endpoint. The partners think the data are good enough to support a filing for approval of the fast-tracked, breakthrough-designated drug later this year but are yet to share the numbers.

Rather, AstraZeneca and Daiichi said the results were clinically meaningful and confirm the efficacy seen in phase 1. In the earlier trial, 60% of HER2+ breast cancer patients responded to the ADC, despite most of them having previously been treated with five or more anticancer regimens such as Roche’s Herceptin and Perjeta.

Phase 2 results in line with those numbers would set AstraZeneca and Daiichi up to position the ADC as an option for HER2+ breast cancer patients who progress following treatment with Roche’s drugs. Current ASCO guidance states patients should start on a combination of Herceptin and Perjeta and move onto Roche’s Kadcyla and later Novartis’ Tykerb as they progress. 

Kadcyla secured its status as the preferred second-line treatment option on the back of a clinical trial that linked it to an overall response rate (ORR) of 44%. Novartis’ Tykerb achieved an ORR of 31% when given with Xeloda in the Kadcyla trial. The study also linked Kadcyla to improved overall survival (OS) of 31 months. It is unclear how DS-8201 compares on that front, as the phase 1 was yet to reach the median OS at the time the data were published. 

The hefty upfront AstraZeneca paid for an even split of the costs and profits from DS-8201 means it may need the results to support blockbuster sales if it is to make a major return on its investment. Whether that is likely may become clearer when the partners share data at an upcoming medical meeting and take DS-8201 through the FDA submission process.