HER2-targeted antibody drug conjugate shows encouraging responses, long-lasting clinical benefit in several tumor types

Reviewed by Danielle Ellis, B.Sc.Jun 5 2023

In a new study of trastuzumab deruxtecan, a HER2-targeted antibody drug conjugate, researchers observed encouraging responses and long-lasting clinical benefit in several tumor types. These data from an interim analysis of the Phase II DESTINY-PanTumor02 study, led by The University of Texas MD Anderson Cancer Center, were presented today at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting.

The treatment achieved an objective response rate (ORR) of 61.3% with a median duration of response (DOR) of 22.1 months in patients with the highest levels of HER2 expression. Across all patients, the ORR was 37.1% with a median DOR of 11.8 months. An ORR of more than 30% was observed in all cancer types except biliary tract (22%) and pancreatic cancers (4%).

According to presenting author Funda Meric-Bernstam, M.D., chair of Investigational Therapeutics, these pan-tumor results show promise in a significant unmet area of clinical need.

These are really notable results in this heavily pretreated population, especially in the gynecological cancer cohorts and in patients with higher levels of HER2 expression."

Funda Meric-Bernstam, M.D., Chair of Investigational Therapeutics

Antibody drug conjugates work by utilizing an antibody to target and bind to a specific protein, in this case HER2, and delivering chemotherapy directly to the cell. Trastuzumab deruxtecan is approved for HER2-expressing breast cancer and is the only antibody drug conjugate approved in the U.S. for HER2-positive gastric cancer and HER2-mutant lung cancer. However, HER2 also is expressed in several other tumor types.

This international open-label study was designed to evaluate the anti-tumor activity of trastuzumab deruxtecan in patients with HER2-expressing locally advanced or metastatic cancers. The trial included 267 patients with cervical, endometrial, ovarian, biliary tract, pancreatic and bladder cancers, as well as other tumors.

The level of HER2 expression was measured by an immunohistochemistry (IHC) test. Seventy-five patients scored IHC 3+, indicating the highest level of HER2 expression, and 125 scored IHC 2+ by central testing. Most patients were female (67%) with an average age of 62 years and a median of two prior lines of therapy. Patients were 61% white, 32.6% Asian and 6.4% other or non-reported ethnicities.

Grade 3 or higher treatment-related adverse events occurred in 38.6% of all patients, the most common being nausea, fatigue and cytopenias. In total, 8.2% of patients discontinued treatment for drug-related adverse events. The safety profile was consistent with previous clinical trials of trastuzumab deruxtecan.

"Our data demonstrate that HER2 expression is actionable in many tumor types. Trastuzumab deruxtecan had compelling clinical activity across tumor types, with prolonged responses and disease stabilization in many patients," Meric-Bernstam said. "This could help provide a new treatment option for these patients with advanced disease and hard-to-treat HER2-positive cancers who currently have very limited or no options."

This trial is ongoing, with several patients still receiving treatment. The progression-free survival and overall survival will be analyzed with further follow-up.

This trial is supported by AstraZeneca in collaboration with Daiichi Sankyo. A full list of collaborating authors and disclosures can be found with the abstract here.