Gilead’s Trodelvy Gives Enhertu a Run for its Money in Metastatic Breast Cancer

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Weeks after AstraZeneca and Daiichi Sankyo were able to move the bar in the treatment of metastatic breast cancer with Enhertu, Gilead Sciences is answering that challenge with Trodelvy.

On Monday, Gilead posted what it called “statistically significant and clinically meaningful” results from a second interim analysis of the Phase III TROPiCS-02 study. The trial was assessing the overall survival (OS) benefits provided by Trodelvy (sacituzumab govitecan-hziy) in patients with HR+/HER2- metastatic breast cancer who received prior endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy.

HR+ and HER2- breast cancer account for approximately 70% of all breast cancer cases and many patients with advanced forms of the disease can develop endocrine resistance. While full overall survival results will be presented at a future medical conference, Gilead said the survival results are encouraging for patients with this form of breast cancer.

Merdad Parsey, chief medical officer of Gilead, said the survival results seen in the second interim analysis are important for the breast cancer community. He said the company is encouraged by the potential of the data and how it can possibly change the course of treatment for breast cancer patients who have limited alternatives.

“We look forward to discussing these results with global health authorities, as pre-treated HR+/HER2- metastatic disease patients currently have limited treatment options and poor quality of life,” Parsey said in a statement.

Trodelvy is a first-in-class antibody-drug conjugate and topoisomerase inhibitor directed at the Trop-2 receptor, which is a protein commonly expressed in multiple types of epithelial tumors, including in more than 90% of breast and bladder cancers.

Gilead has submitted a supplemental Biologics License Application to the U.S. Food and Drug Administration based on data from the Phase III TROPiCS-02 study. Earlier this year, the company presented data from the study that showed Trodelvy met its primary endpoint in the clinical trial. It demonstrated a statistically significant improvement in progression-free survival (PFS) versus physician’s choice of chemotherapy.

Though Trodelvy’s target is different from Enhertu’s, both drugs provide viable options for breast cancer patients. The Phase III Enhertu study was the first HER2-directed therapy that showed a “significant and clinically meaningful survival benefit in previously treated patients with HER2 low unresectable and/or metastatic breast cancer,” AstraZeneca and Daiichi Sankyo stated. 

Full overall survival benefits of Enhertu were not reported in the announcement, but in June, the companies noted a 49% OS improvement with the drug. That was a six-month improvement over chemotherapy alone.

Gilead gained Trodelvy through its $21 billion acquisition of Immunomedics. It has previously been approved for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer, as well as adult patients with locally advanced or metastatic urothelial cancer.

Gilead also announced that it reached a $280 million agreement with Everest Medicines to secure all development and commercialization rights for Trodelvy in much of the Asian market, including Greater China, South Korea, Singapore, Indonesia, Philippines, Vietnam, Thailand, Malaysia and Mongolia. Everest Medicine gained the rights to Trodelvy through a previous partnership with Immunomedics.

In addition to the upfront payment, Everest is eligible to receive up to $175 million in potential additional payments upon achievement of certain regulatory and commercial milestones, Gilead said.

“Trodelvy is the cornerstone of our solid tumor portfolio, and we are committed to bringing this transformative therapy to as many patients as possible. We look forward to rapidly advancing our development program in Asia and to realizing the clinical potential of Trodelvy across diverse tumor types,” Bill Grossman, president of oncology clinical research at Gilead said in a statement.

In mainland China and Singapore, Trodelvy has been approved for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. The company is seeking approval in Hong Kong, South Korea and Taiwan.