Trastuzumab Deruxtecan Shows Clinical Activity in HER2+ Solid Tumors


Funda Meric-Bernstam, MD, discusses the phase 2 DESTINY-PanTumor02 trial of fam-trastuzumab deruxtecan-nxki for the treatment of patients with HER2-expressing solid tumors.

Funda Meric-Bernstam, MD, chair of the Department of Investigational Cancer Therapeutics at MD Anderson Cancer Center, discusses the phase 2 DESTINY-PanTumor02 trial (NCT04482309) of fam-trastuzumab deruxtecan-nxki (Enhertu) for the treatment of patients with HER2-low breast cancer, HER2-positive breast cancer, HER2-positive gastric cancer, and HER2-mutant lung cancer.

Trastuzumab deruxtecan is a potent antibody-drug conjugate. The agent has become a standard of care for a variety of HER2-expressing solid tumors.

This open-label, multicenter, multicohort, phase 2 study is assessing the primary end point of investigator-assessed confirmed objective response rate per RECIST v1.1, along with the secondary end points of duration of response, disease control rate, progression-free survival, overall survival, safety, pharmacokinetics, and immunogenicity.

According to findings presented at the American Society of Clinical Oncology Annual Meeting 2023, demonstrated clinically meaningful activity trastuzumab deruxtecan demonstrated clinically meaningful activity across a wide range of HER2 expressing solid tumors.


0:10 | Overall, we enrolled 276 patients, and showed that our investigator assessed objective response rate, which was the primary end point, was 37%. This is, of course, a heavily pretreated patient population with a median of 2 prior lines of therapy. In addition, we saw that these were durable responses. Patients had a median duration of response of 11.8 months, and the objective response rate was also confirmed with central review.

0:40 | We looked across tumor types and we saw that there were responses across a variety of tumors with objective response rates that were especially compelling in the gynecological tumors, but also very clinically meaningful in patients with biliary cancer and bladder cancer. The 1 cohort where we had less tumor activity was in pancreatic cancer. That study arm was closed a little early at 25 patients. We had 1 investigator assess objective response, and we also had a central review which actually showed a 12% response rate with 3 responses. Notably, however, in that patient population, around 68% of the patients had stable disease as well. This is a study that was conducted internationally, and we saw that with this study, the safety was similar to what we know.

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