Enhertu Demonstrates Positive Results Across Multiple HER2-Expressing Tumor Types

Konstantin Yuganov / stock.adobe.com

Trastuzumab deruxtecan (Enhertu) from AstraZeneca and Daiichi Sankyo met the prespecified target for objective response rate (ORR), demonstrating durable response across multiple human epidermal growth factor receptor 2 (HER2)-expressing advanced solid tumors in patients who were heavily treated.

Trastuzumab deruxtecan was specifically engineered to be a HER2-directed antibody drug conjugate.

“[Trastuzumab deruxtecan] has already demonstrated its potential to improve outcomes for patients with HER2-targetable breast, gastric, and lung cancers, and these positive initial results in other tumor settings with significant unmet need are very encouraging. The DESTINY-PanTumor02 (NCT04482309) results mark an important step forward in our understanding of the potential role of [trastuzumab deruxtecan] across multiple HER2-expressing tumor types,” Cristian Massacesi, MD,chief medical officer and oncology chief development officer at AstraZeneca, said in a statement.

The DESTINY-PanTumor02 phase 2 trial evaluated the efficacy and safety of trastuzumab deruxtecan in individuals with locally advanced, unresectable, or metastatic previously treated, HER2-expressing solid tumors that were not eligible for curative therapy. This included biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and rare cancers.

The primary endpoint included investigator-assessed confirmed ORR. Investigator-assessed duration of response was the key secondary endpoint.

Secondary endpoints also included disease control rate, overall survival, pharmacokinetics progression-free survival, safety, and tolerability.

“The clinically meaningful responses seen in the DESTINY-PanTumor02 trial reaffirm our belief in the potential of [trastuzumab deruxtecan] across multiple HER2-expressing cancers. The results seen so far across multiple cohorts of the trial will inform next steps of our broad development program as we look to bring this important medicine to as many patients as quickly as possible,” Ken Takeshita, MD, global head of research and development at Daiichi Sankyo, said in the statement.

Investigators enrolled 268 individuals at multiple sites across Asia, Europe, and North America. The safety profile of the drug was consistent with other trials of trastuzumab deruxtecan, with no new safety signals identified.

The data from the study will be presented at an upcoming medical meeting and will be shared with global regulatory authorities.

Trastuzumab deruxtecan consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor, exatecan derivative, and a stable tetrapeptide-based cleavable linker.

It is approved in more than 40 countries for the treatment of adults with metastatic or unresectable HER2-positive breast cancer and received 1 or more prior anti-HER2-based regimens in the adjuvant, metastatic, or neoadjuvant setting, and have developed disease recurrence during or within 6 months of completing therapy.

Additionally, it was approved in more than 30 countries for the treatment of adults with metastatic or unresectable HER2-low breast cancer who developed disease recurrence during or within 6 months of completing adjuvant chemotherapy or received prior systemic therapy in the metastatic setting.

A comprehensive global development program is also under way for the efficacy and safety of trastuzumab deruxtecan as a monotherapy across multiple HER2-targetable cancers.

Reference

Enhertu showed clinically meaningful and durable responses across multiple HER2-expressing tumour types in DESTINY-PanTumor02 phase II trial. News release. AstraZeneca. March 6, 2023. Accessed March 14, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/enhertu-destiny-pantumor02-shows-positive-results.html