MSD/Seagen Initiates Phase 3 Clinical Trial of HER2-Targeted Small Molecule Inhibitor Tucatinib for Breast Cancer in China

By | Pharma Observer

On October 18, the China Drug Clinical Trial Registration and Information Disclosure Platform indicated that MSD and Seagen, Inc., among others, have initiated a Phase 3 clinical trial in China evaluating tucatinib for the treatment of locally advanced or metastatic HER2-positive breast cancer. Tucatinib is a highly selective small-molecule oral inhibitor targeting HER2, and has been approved in the United States for the treatment of adult patients with advanced HER2-positive breast cancer. The drug has previously been granted Fast Track designation, Orphan Drug designation, and Breakthrough Therapy designation by the FDA.

Screenshot source: Drug Clinical Trial Registration and Information Disclosure Platform

Among patients with breast cancer, many overexpress human epidermal growth factor receptor 2 (HER2). The HER2 protein promotes cancer cell growth, significantly affecting patient treatment and prognosis. Published data indicate that over 25% of women with metastatic HER2-positive breast cancer develop brain metastases.

Tucatinib is an oral tyrosine kinase inhibitor developed by Seagen that exhibits high specificity for HER2, with minimal inhibitory activity against EGFR, another member of the human epidermal growth factor receptor family. In April 2020, the FDA approved tucatinib for use in combination with trastuzumab and capecitabine for the treatment of adult patients with previously treated, advanced unresectable or metastatic HER2-positive breast cancer.

In September 2020, MSD and Seagen, Inc. entered into a collaboration under which MSD obtained exclusive commercialization rights for tucatinib in Asia, the Middle East, and Latin America, as well as other regions outside the United States, Canada, and Europe, for the treatment of HER2-positive cancers. Under this collaboration, Seagen, Inc. received a $125 million upfront payment and is eligible for up to $65 million in milestone payments.

A randomized, double-blind, international, multicenter Phase 3 clinical trial (HER2CLIMB-02) has been initiated in China to evaluate and compare the efficacy and safety of tucatinib or placebo in combination with trastuzumab emtansine for the treatment of unresectable locally advanced or metastatic HER2-positive breast cancer.

According to the Chinese Drug Clinical Trial Registration and Information Publicity Platform, Professor Xu Binghe from the Cancer Hospital, Chinese Academy of Medical Sciences, will serve as the principal investigator for this trial. The study will be conducted at 24 clinical trial sites across China, with a planned enrollment of 105 patients. The primary endpoint is to compare the progression-free survival (PFS) between the two treatment arms, while the key secondary endpoints are to compare the overall survival (OS) and objective response rate (ORR) between the two treatment groups.

Notably, the Phase 3 HER2CLIMB trial of tucatinib was recognized by the American Society of Clinical Oncology (ASCO) as one of the 20 most important clinical studies in oncology in 2020. The study demonstrated that adding the HER2-targeted therapy tucatinib to the standard-of-care regimen of trastuzumab and capecitabine significantly improved patients' progression-free survival (PFS), reducing the risk of disease progression or death by 46%. Furthermore, the triplet regimen also improved patients' overall survival (OS), reducing the risk of death by 34%.

References:

[1] Chinese Clinical Trial Registration and Information Disclosure Platform. Retrieved Oct 18, 2021, from http://www.chinadrugtrials.org.cn/clinicaltrials.searchlist.dhtml

[2] FDA Approves First New Drug Under International Collaboration, A Treatment Option for Patients with HER2-Positive Metastatic Breast Cancer. Retrieved April 17, 2020, from https://www.fda.gov/news-events/press-announcements/fda-approves-first-new-drug-under-international-collaboration-treatment-option-patients-her2

[3] Seattle Genetics and Merck Announce Two Strategic Oncology Collaborations. Retrieved September 14, 2020, from https://www.merck.com/news/seattle-genetics-and-merck-announce-two-strategic-oncology-collaborations/

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