Salvatore Siena, MD, professor of medical oncology at Universita degli Studi di Milano and director of Niguarda Cancer Center at Grande Ospedale Metropolitano Niguarda in Italy, discusses the rationale for the ​phase 2 DESTINY-CRC01 trial in metastatic colorectal cancer (mCRC).

HER2-targeted therapy has demonstrated success in the metastatic setting as a treatment option for patients with HER2-positive CRC, says Siena. 

As such, ​the antibody-drug conjugate (ADC) fam-trastuzumab deruxtecan-nxki (Enhertu) appeared to be a rational agent to evaluate in this space, Siena explains. The potent compound includes an 8:1 ratio of the topoisomerase I inhibitor payload and HER2-directed monoclonal antibody, says Siena. 

Notably, CRC cells are sensitive to topoisomerase I inhibitors, such as irinotecan, which is ​a common treatment in this space, Siena concludes.

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Salvatore Siena, MD, discusses the rationale for the phase 2 DESTINY-CRC01 trial in metastatic colorectal cancer.
 


  Dr. Siena on the Rationale for the DESTINY-CRC01 in Metastatic CRC

Salvatore Siena, MD, professor of medical oncology at Universita degli Studi di Milano and director of Niguarda Cancer Center at Grande Ospedale Metropolitano Niguarda in Italy, provides an overview of the DESTINY-CRC01 trial ​in HER2-positive metastatic colorectal cancer (CRC).

The phase 2 trial evaluated fam-trastuzumab deruxtecan​-nxki (Enhertu), says Siena. Trastuzumab deruxtecan isa​n antibody-drug conjugate with a cleavable tetrapeptide-based linker and a topoisomerase 1 inhibitor that has demonstrated activity in HER2-expressing cancers, Siena adds.

DESTINY-CRC01 enrolled patients into 3 cohorts, explains Siena. Cohort A enrolled 53 patients with either primary tumors or metastasized tumors expressing HER2 to a level of immunohistochemistry (IHC) 3+ or 2+ and in-situ hybridization (ISH)–positive, Siena explains. ​Cohort B evaluated 7 patients with IHC 2+ but in-situ hybridization–negative tumors. Finally, cohort C, made up of 18 patients, included those with IHC 1+ disease, Siena concludes.

Salvatore Siena, MD, provides an overview of the DESTINY-CRC01 trial ​in DESTINY-CRC01 trial in HER2-positive metastatic colorectal cancer.

Salvatore Siena, MD

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