By: Alaric DeArment
The companies announced the partnership in March to develop trastuzumab deruxtecan, for which they plan to file approval later this year based on the successful Phase II study.
The growing field of antibody-drug conjugates may soon get a new member with positive Phase II data in breast cancer.
Anglo-Swedish drugmaker AstraZeneca and Japan-based Daiichi Sankyo said Wednesday that its Phase II DESTINY-Breast01 study of trastuzumab deruxtecan met the primary endpoint of overall response rate among patients with refractory HER2-positive metastatic breast cancer. The company did not disclose what the response rate was, but stated that it confirmed the “unprecedented” clinical activity of the drug shown in a Phase I study published last month. The Phase II results announced Wednesday were among patients who had failed or discontinued treatment with another antibody-drug conjugate, Roche’s Kadcyla (ado-trastuzumab emtansine).
The companies said they plan to file for regulatory approval based on the Phase II results in the second half of this year. Shares of AstraZeneca were up more than 1 percent on the London Stock Exchange following the news. Daiichi Sankyo’s shares were mostly flat on the Tokyo Stock Exchange. The companies announced a partnership to develop the drug, which uses Daiichi Sankyo’s antibody-drug conjugate technology, at the end of March. The deal included a $1.35 billion upfront payment from AstraZeneca, plus up to $5.55 billion in potential milestone payments.
Results of the Phase I trial were published in two manuscripts in The Lancet last week. In one manuscript, the response rate was 59.5 percent among 115 patients, while disease control rate was 93.7 percent. The median progression-free survival was 22.1 months, while the overall survival median was not yet reached, with 55 patients – representing 48 percent of the total – remaining on treatment. In the second manuscript, with data on 44 patients, the ORR and DCR were 43.2 percent and 79.5 percent, respectively.
Both trastuzumab deruxtecan and Kadcyla are derived from Roche’s Herceptin (trastuzumab), a HER2-targeting monoclonal antibody. Currently, there are four Herceptin biosimilars approved by the Food and Drug Administration. The first to win approval was Mylan’s Ogivri (trastuzumab-dkst), in December 2017, while the latest is Pfizer’s Trazimera (trastuzumab-qyyp), approved in March.
Antibody-drug conjugates, also known as ADCs, consist of a monoclonal antibody with an attached pharmaceutical payload. In addition to Kadcyla, other approved ADCs include Seattle Genetics’ Adcetris (brentuximab vedotin), for Hodgkin’s lymphoma and certain T-cell lymphomas; and two from Pfizer, namely Mylotarg (gemtuzumab ozogamicin), for acute myeloid leukemia, and Besponsa (inotuzumab ozogamicin), for acute lymphoblastic leukemia. Seattle Genetics also has numerous other ADCs in its pipeline.
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.