AstraZeneca and Daiichi Sankyo’s ADC Enhertu Shows Promising Activity in HER2-Expressing Cancers Including NSCLC

On the 26th, Enhertu (fam-trastuzumab deruxtecan-nxki, DS-8201), a HER2-targeted antibody-drug conjugate (ADC) co-developed by Daiichi Sankyo and AstraZeneca, reduced tumor size in 55.6% of patients with non-small cell lung cancer (NSCLC) in a Phase 1 clinical trial involving patients with previously treated HER2-overexpressing cancers. Additionally, on the 26th, Japan’s Ministry of Health, Labour and Welfare (MHLW) announced its approval of Enhertu for the treatment of patients with unresectable HER2-positive or metastatic breast cancer.

HER2 is a protein belonging to the human epidermal growth factor receptor family. It is overexpressed in various cancers, including breast cancer, ovarian cancer, gastric cancer, and lung cancer. HER2 mediates cell growth, differentiation, and survival, and can promote the aggressive spread of cancer cells. Compared with HER2-negative cancers, HER2-positive tumors are more aggressive and are associated with shorter survival times, poorer overall survival rates, a higher risk of recurrence, and involvement of central nervous system disorders.

Enhertu leverages Daiichi Sankyo’s proprietary antibody-drug conjugate (ADC) technology, linking the humanized HER2 antibody trastuzumab to a novel topoisomerase I inhibitor via a tetrapeptide linker. This mechanism targets cancer cells and delivers the drug intracellularly. Compared with conventional chemotherapy, this class of novel agents can reduce the toxic side effects associated with chemotherapeutic drugs. Enhertu is currently under investigation for the treatment of various HER2-expressing cancers, including breast cancer, gastric cancer, non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and in patients with low HER2 expression. Last year, the U.S. FDA approved Enhertu for the treatment of patients with HER2-positive, locally advanced or metastatic breast cancer who had previously received HER2-targeted therapies such as trastuzumab and pertuzumab.

A total of 60 patients with HER2-overexpressing or mutated cancers who had received prior treatment participated in this Phase 1 clinical study, including 18 patients with non-small cell lung cancer (NSCLC), 20 patients with colorectal cancer (CRC), and several patients with other tumor types. Data from the trial showed that treatment with Enhertu resulted in tumor shrinkage in 28.3% of patients and achieved a median progression-free survival (PFS) of 7.2 months. Among them, NSCLC patients had the highest objective response rate, with 55.6% experiencing tumor shrinkage and a median duration of response of 10.7 months. The efficacy was more pronounced in NSCLC patients harboring HER2 mutations, with 72.7% of this group achieving a response to Enhertu treatment. The median PFS for all NSCLC patients reached 11.3 months.

Furthermore, another study published in Cancer Discovery found that treatment with Enhertu achieved partial response in patients with non-small cell lung cancer (NSCLC) whose disease had progressed despite prior treatment with another antibody-drug conjugate (ADC), Kadcyla, reducing tumor size by 70%.

“We are very pleased with the results of this preliminary study,” said Bob Li, M.D., an oncologist at Memorial Sloan Kettering Cancer Center. “Enhertu has shown early promise in changing the standard of care for patients with HER2-overexpressing or HER2-mutant cancers, and we look forward to advancing this important research in future clinical trials.”

References:

[1] Astra, Daiichi's Enhertu shows early promise in HER2 lung cancer, Retrieved March 25, 2020, from https://www.fiercebiotech.com/research/astra-daiichi-s-enhertu-shows-early-promise-her2-lung-cancer

[2] ENHERTU® Approved in Japan for Treatment of Patients with HER2 Positive Unresectable or Metastatic Breast Cancer, Retrieved March 25, 2020, from https://www.businesswire.com/news/home/20200325005042/en

Original Title: Express | AstraZeneca/Daiichi Sankyo’s Blockbuster ADC for Non-Small Cell Lung Cancer Yields Positive Data

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