Editing Daiichi Sankyo Company, Limited (section)

=== HER3-DXd ===
Approximately 10% to 15% of patients with NSCLC in the US and Europe and 30% to 40$ of those in Asia have an EGFR-activating mutation. In these patients EGFR (Epidermal Growth Factor Receptor) -targeted tyrosine kinase inhibitors (TKI) result in high response rate and can provide extended disease control. However, relapse is typical with the development of resistance to EGFR TKI treatment, with the mechanisms associated with resistance being diverse, and a significant amount of which being unidentified.

Given that resistance mechanisms to EGFR TKIs are diverse and the efficacy of chemotherapy is limited, there is a need to develop novel treatment approaches for previously treated EGFR-mutated NSCLC that provide <u>salvage therapy</u>* across a broad spectrum of resistance-associated genomic alteration.

HER3 is expressed across a variety of malignant solid tumors and has been found in 83% of <u>primary</u>** NSCLC tumors. HER3 overexpression is associated with metastatic progression and decreased relapse-free survival in patients with NSCLC. EGFR-mutated NSCLC is associated with higher expression of HER3 compared to EGFR <u>wild-type</u>*** NSCLC.

HER3-DXd is a novel ADC, which specifically targets HER3. In a study 57 patients recieving HER3-DXd the <u>objective response rate</u>**** was found to be 39% and the median <u>progression-free survival</u>***** was 8.2 months. Responses were also observed in patients with known and unknown EGFR TKI resistance mechanisms<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401524/</ref>

A list of HER3-DXd drugs currently in clinical trials can be found [https://www.daiichisankyo.com/files/rd/pipeline/index/pdf/pipeline2304_en.pdf here] in green.


<nowiki>*</nowiki>treatment recieved after standard treatment has failed

<nowiki>**</nowiki> used to describe the first, or primary tumor, the one from which metastatsis (development of secondary tumors) occurs

<nowiki>***</nowiki> non-mutated gene

<nowiki>****</nowiki> The total number of people whose cancer has either gone away (complete response) or shrunk (partial response)<ref name=":0">https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/clinical-trial-results/what-do-clinical-trial-results-mean-0</ref>

<nowiki>*****</nowiki> Time between treatment aimed at shrinking or controlling cancer, and signs that it has started to grow again<ref name=":0" />