Dr. Raghav on Potential Combinations With Trastuzumab Deruxtecan in HER2+ CRC

Kanwal P.S. Raghav, MBBS, MD, associate professor, Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, medical director, Division of Ambulatory Treatment Centers, The University of Texas MD Anderson Cancer Center, discusses potential combinations with fam-trastuzumab deruxtecan-nxki (Enhertu) in HER2-positive colorectal cancer (CRC).

Trastuzumab deruxtecan is an antibody-drug conjugate that acts as a targeted chemotherapeutic agent, Raghav says. The drug delivers a high concentration of an active cytotoxic topoisomerase I inhibitor payload.

Although the agent is not yet approved for use in HER2-positive CRC, combination strategies are a promising potential strategy to increase the sensitivity of the chemotherapy payload, Raghav explains. For example, trastuzumab deruxtecan is being evaluated in combination with AZD6738, an ATP inhibitor, in the ongoing phase 1 DASH trial (NCT04704661). AZD6738 is a DNA damage repair inhibitor, which can increase cell death.

Additionally, trastuzumab deruxtecan is being evaluated in combination with immunotherapy or other DNA damage repair inhibitors in ongoing or developing clinical trials, Raghav concludes.