1st patient dosed in trial of Enhertu for HER2 endometrial cancer
Researchers studying use of therapy in combination with other treatments
A Phase 3 clinical trial of Enhertu, a therapy developed by Daiichi Sankyo and AstraZeneca, has begun dosing its first patient with endometrial cancer, a type of gynecological cancer. The study focuses on patients whose tumors express the HER2 protein.
In the DESTINY-Endometrial01 clinical trial (NCT06989112), researchers are studying the use of Enhertu (trastuzumab deruxtecan) in combination with other treatments for endometrial cancer. This trial is specifically focused on people with primary advanced or recurrent endometrial tumors that produce the HER2 protein and still have working DNA repair systems, which may influence how well the treatment works or how the disease responds.
“The DESTINY-Endometrial01 trial will help us better understand the role of Enhertu in combination with immunotherapy as a potential treatment strategy to help improve outcomes compared to the current standard of care in this specific gynecological cancer setting,” Mark Rutstein, MD, head of therapeutic area oncology development at Daiichi Sankyo, said in a company press release.
U.S. regulators have approved Enhertu as a second-line treatment for certain types of breast cancer and other HER2-positive, treatment-resistant solid tumors, including those with no other satisfactory options.
Researchers to look for differences in length of survival without disease progression
In the trial, Enhertu will be given together as into-the-vein, or intravenous, infusions with Keytruda (pembrolizumab), an approved immunotherapy, or the experimental antibody rilvegostomig. The researchers will compare the results in these treatment groups to a control group receiving Keytruda plus standard platinum-based chemotherapy. Participants will remain on treatment until the disease progresses or they meet other discontinuation criteria.
The researchers will look for differences between treatment groups in the length of survival without disease progression, up to approximately 45 months, or nearly four years, as well as the length of overall survival. The study is currently recruiting in Louisiana, South Korea, and Taiwan, with multiple other sites expected to join.
Endometrial cancer starts in the endometrium, the inner lining of the uterus. It is the most common form of gynecological cancer and typically progresses slowly. In some cases, cells in endometrial tumors, and other types of cancer, produce too much of a protein called HER2, short for human epidermal growth factor receptor 2, or have extra copies of the HER2 gene.
HER2 plays a role in regulating cell growth and division, so when it’s overproduced, it can drive the rapid and uncontrolled cell proliferation that characterizes cancer. Endometrial cancers with high levels of HER2, known as HER2-positive tumors, are often more aggressive and linked to worse outcomes than HER2-negative cancers.
Enhertu has shown therapeutic effects in HER2 cancers
No approved first-line therapies for endometrial cancer currently target HER2, according to the press release. Enhertu is designed to block the growth and spread of cancer cells by targeting those that produce the HER2 protein. As an antibody-drug conjugate, it combines a HER2-specific antibody with a potent chemotherapy agent. Once the antibody binds to HER2 on the surface of a cancer cell, the drug is delivered directly into the cell, helping to kill it from within. This targeted approach aims to maximize the treatment’s impact on tumors while minimizing damage to healthy cells.
In several clinical trials, Enhertu has shown therapeutic effects in HER2-positive cancers, as well as breast cancers with lower HER2 levels. An ongoing Phase 2 trial (NCT04482309), dubbed DESTINY-PanTumor02, is testing the medication in endometrial tumors and several other cancers.
Primary results from DESTINY-PanTumor02 demonstrated that 57.5% of participants with endometrial cancer responded to the medication. This response rate was higher (84.6%) in the subset of participants with higher levels of HER2 on the surface of cancer cells.
“Following the positive results in the endometrial cancer cohort of DESTINY-PanTumor02, which contributed to a tumor-agnostic approval for previously treated patients with HER2-positive metastatic tumors in several regions, we are initiating this first phase 3 trial of Enhertu in the first-line setting of advanced endometrial cancer,” Rutstein said.
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