Trastuzumab Deruxtecan Achieves 97.3% Disease Control Rate in Heavily Pretreated HER2-Positive Metastatic Breast Cancer, Meets Primary Endpoint in Pivotal Trial

Today, AstraZeneca and Daiichi Sankyo jointly announced that [fam-] trastuzumab deruxtecan (DS-8201), an antibody-drug conjugate (ADC) co-developed by the two companies, met its primary endpoint in the pivotal Phase 2 DESTINY-Breast01 trial in patients with HER2-positive metastatic breast cancer. The press release highlighted that DS-8201 has the potential to become a new treatment option for breast cancer patients who have received at least two prior HER2-targeted therapies.

HER2-positive breast cancer is an aggressive disease that affects approximately 20% of patients with breast cancer. Patients with HER2-positive early-stage breast cancer who do not achieve a pathological complete response (pCR) after neoadjuvant therapy may experience a poorer prognosis. The goal of treatment for early-stage breast cancer is to provide patients with the best possible chance of cure. Although medical advancements have brought us closer to this goal, many patients still face a risk of recurrence in the long term.

DS-8201 is an innovative antibody-drug conjugate (ADC) targeting HER2. It links trastuzumab, a fully humanized monoclonal antibody targeting the HER2 receptor, to a novel topoisomerase I inhibitor via a tetrapeptide linker. This ADC enables the attachment of a higher number of cytotoxic molecules to the antibody, thereby potentially enhancing its tumor-killing efficacy. In 2017, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation to this ADC for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer. In October of this year, the FDA accepted the Biologics License Application (BLA) for DS-8201 and granted it Priority Review status.

▲DS-8201 Significantly Reduces Tumor Size in Patients (Image Source: Reference [2])

The DESTINY-Breast01 study is a pivotal Phase 2 clinical trial. The 184 patients enrolled in the trial had received a median of six prior therapies, including ado-trastuzumab emtansine (T-DM1), trastuzumab, and pertuzumab. Trial results demonstrated that patients treated with DS-8201 achieved an objective response rate (ORR) of 60.9% and a disease control rate (DCR) of 97.3%. The median duration of response (DOR) was 14.8 months, and the median progression-free survival (PFS) was 16.4 months.

▲ PFS Data in Patients Treated with DS-8201 (Image Source: Reference [2])

“We observed clinically meaningful and significant improvements in patients in the DESTINY-Breast01 trial, demonstrating the potential of DS-8201 to become a new standard of care for breast cancer patients,” said Dr. José Baselga, Executive Vice President of Oncology R&D at AstraZeneca. “Patients with HER2-positive advanced breast cancer enrolled in this trial had received multiple prior therapies, and we are very satisfied with the therapeutic efficacy of DS-8201.”

“The results of this pivotal trial are consistent with the previous research data on DS-8201,” said Dr. Antoine Yver, Executive Vice President of Oncology Research and Development at Daiichi-Sankyo and Global Head. “This further demonstrates the efficacy of our HER2-targeted antibody-drug conjugate in treating patients with HER2-positive metastatic breast cancer.”

References:

[1] [Fam]-Trastuzumab Deruxtecan Achieved a Tumor Response of 60.9% in Pivotal Phase II HER2-positive Metastatic Breast Cancer Trial , Retrieved December 11, 2019, from https://www.businesswire.com/news/home/20191211005425/en

[2] Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer，Retrieved December 11, 2019 from https://www.nejm.org/doi/full/10.1056/NEJMoa1914510?query=featured_home

Original Title: Express | 97.3% Disease Control Rate in Refractory Breast Cancer! Blockbuster ADC Therapy Achieves Primary Clinical Endpoint

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