Daiichi Sankyo’s HER2-Targeted ADC Enhertu Approved in Japan with 64.1% Objective Response Rate in Heavily Pretreated Metastatic Breast Cancer

March 26, 2020/Bio ValleyBIOON/--Daiichi Sankyo recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Enhertu (trastuzumab deruxtecan, DS-8201) for the treatment of HER2-positive, unresectable or metastatic cancer that has relapsed after prior chemotherapy.Breast CancerPatients (limited to those who are refractory to or intolerant of standard therapy). In the United States, Enhertu received accelerated approval in December 2019 for adult patients with HER2-positive metastatic breast cancer who have previously received two or more anti-HER2-based regimens in the metastatic setting.

This approval is based on the results of the pivotal Phase 2 DESTINY-Breast01 trial. This was a key, single-arm, open-label, global, multicenter, two-part study evaluating the safety and efficacy of Enhertu (5.4 mg/kg) as monotherapy in patients with HER2-positive, unresectable and/or metastatic breast cancer. The study enrolled a total of 184 patients from more than 100 clinical sites worldwide (including 30 Japanese female patients). All patients had previously received two or more HER2-targeted regimens; the median number of prior therapies for metastatic disease was 6 (range: 2–27). Prior therapies included trastuzumab emtansine (T-DM1; 100% of patients), trastuzumab (100%), pertuzumab (65.8%), other anti-HER2 therapies (54.3%), hormonal therapy (48.9%), and other systemic treatments (99.5%). The primary endpoint of the study was objective response rate (ORR).

The results showed that among 167 evaluable patients, 107 achieved disease remission, i.e.,The ORR for Enhertu monotherapy (5.4 mg/kg) was 64.1% (95% CI: 56.3–71.3).、Median Duration of Response (DOR) was 14.8 monthsAs of the data cutoff date of March 21, 2019, a total of 26 Japanese female patients were included in the ORR analysis. The safety and tolerability profile of Enhertu in this study was consistent with that observed in the Phase I trial.

Wataru Takasaki, Head of R&D in Japan and Head of Oncology Function at Daiichi Sankyo, stated: “We are pleased to bring our first antibody-drug conjugate (ADC) product, Enhertu, to patients with HER2-positive metastatic breast cancer in Japan. The drug has demonstrated impressive results in patients with HER2-positive metastatic breast cancer who had previously received multiple therapies, with the majority of patients benefiting from the treatment and a median duration of response exceeding 14 months. Enhertu is also the company’s...”Tumor"The second innovative therapy in our pipeline to gain approval in Japan marks a milestone."

Approximately 20% of breast cancer cases are HER2-positive. Despite therapeutic advances and the approval of multiple novel agents in recent years, there remains a significant unmet clinical need among patients with advanced HER2-positive metastatic breast cancer. The disease remains incurable, and patients ultimately experience disease progression after receiving currently available therapies.

HER2 is a tyrosine kinase receptor growth-promoting protein present on the surface of certain cancer cells and is associated with aggressive disease and poorer prognosis in breast cancer patients. Tumor cells are typically tested for HER2 expression using either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). IHC results are reported as IHC 0, IHC 1+, IHC 2+, or IHC 3+. The presence of IHC 3+ and/or FISH amplification is considered HER2-positive. Currently, there are no targeted therapies for HER2 FISH-negative, IHC 2+, or IHC 1+TumorHER2-targeted drugs.

Enhertu (trastuzumab deruxtecan, DS-8201) is a next-generation antibody-drug conjugate (ADC) that links trastuzumab, a humanized monoclonal antibody targeting HER2, to a novel topoisomerase I inhibitor exatecan derivative (DX-8951 derivative, DXd) via a tetrapeptide linker. This enables targeted delivery of the cytotoxic agent into cancer cells, thereby reducing systemic exposure to the cytotoxic agent compared with conventional chemotherapy.

March 2019,AstraZenecaReached an agreement with Daiichi Sankyo for a total value of up to $6.9 billion in immunologyTumorAcademic collaboration to jointly develop Enhertu for the treatment of patients with various cancers characterized by HER2 expression or HER2 mutations, including gastric cancer, colorectal cancer, and lung cancer, as well as HER2-low breast cancer. Under the agreement, both parties will jointly develop and commercialize Enhertu globally, with Daiichi Sankyo retaining exclusive rights in the Japanese market and assuming full responsibility for manufacturing and supply.

Pharmaceutical market research firm EvaluatePharma previously predicted that Enhertu’s sales would reach $2 billion in 2024 after its launch. (Bioon.com)

Original Source: ENHERTU®approved in Japan for Treatment of Patients with HER2 Positive Unresectable or Metastatic Breast Cancer