Trastuzumab Deruxtecan Gets FDA Priority Review for Metastatic HER2-Positive Breast Cancer

The U.S. Food and Drug Administration (FDA) has granted priority review to the application seeking trastuzumab deruxtecan‘s (DS-8201) approval for the treatment of metastatic HER2-positive breast cancer.

The agency has set a Prescription Drug User Fee Act action date for the second quarter of 2020. By then, it must decide whether to approve trastuzumab deruxtecan for this indication.

Developed by AstraZeneca and Daiicho Sankyo, trastuzumab deruxtecan is an investigational antibody-drug conjugate composed of the anti-cancer HER2-targeting antibody trastuzumab bound to an investigational cancer-killing agent called deruxtecan (a derivative of exatecan).

Once the antibody binds to a cell positive for HER2, it releases the toxic compound, killing the cancer cell without harming healthy cells. The FDA had previously granted fast track and breakthrough therapy designation to trastuzumab deruxtecan.

The biologics license application the companies submitted to the FDA is based on data from a pivotal Phase 1 trial (NCT02564900) and the Phase 2 DESTINY-Breast01 trial (NCT03248492).

Findings from the Phase 1 trial, published in The Lancet Oncology, showed that trastuzumab deruxtecan led to unprecedented clinical activity without significant side effects in a group of 115 women diagnosed with HER2-positive breast cancer.

In this trial, patients had received a median of seven prior treatments, including several HER2-targeted therapies, but 60% still responded to trastuzumab deruxtecan, and 94% had their disease stabilized for a considerable period of time.

Responses lasted for a median of 20.7 months, and patients remained alive and without signs of disease worsening for 22.1 months. Similar response rates were observed among the 253 women with inoperable and/or metastatic HER2-positive tumors who participated in DESTINY-Breast01, confirming the previous findings of the Phase 1 trial.

AstraZeneca and Daiichi Sankyo are planning to present the full data from DESTINY-Breast01 at the San Antonio Breast Cancer Symposium in December.

“Trastuzumab deruxtecan has the potential to transform the treatment landscape for patients with HER2-positive metastatic breast cancer who have limited treatment options today. This Priority Review draws on the strength and the consistency of results seen in the Phase 1 and Phase 2 trials and is a critical step on the journey to deliver this potential new medicine to patients,” José Baselga, executive vice president of oncology research and development at AstraZeneca, said in a press release.

In September, Daiichi Sankyo submitted a similar application to the Japanese regulatory authority, which has also granted SAKIGAKE designation to trastuzumab deruxtecan for the treatment of advanced HER2-positive gastric or gastroesophageal junction cancer. SAKIGAKE is similar to breakthrough therapy designation in the United States.

“We are pleased that the FDA has accepted the application and granted Priority Review, as we believe trastuzumab deruxtecan has the potential to redefine the treatment of patients with HER2-positive metastatic breast cancer. Following the recent regulatory submission in Japan, we look forward to working closely with regulatory authorities to bring trastuzumab deruxtecan to patients in the U.S. and Japan as soon as possible,” said Antoine Yver, executive vice president and global head of oncology research and development at Daiichi Sankyo.