Dr. Raghav on the Rationale for the DESTINY-CRC02 Trial in HER2+ mCRC

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 the rationale for the ongoing phase 2 DESTINY-CRC02 trial (NCT04744831) in HER2-overexpressing metastatic colorectal cancer (mCRC). 

The study schema for the DESTINY-CRC02 trial will be presented during the 2022 Gastrointestinal Cancers Symposium during a trial in progress poster presentation. The study represents a logical continuation of the phase 2 DESTINY-CRC01 trial (NCT03384940), which evaluated the efficacy of fam-trastuzumab deruxtecan-nxki (Enhertu) in patients with HER2-expressing mCRC who did not harbor RAS or BRAF mutations, Raghav says.

The DESTINY-CRC01 trial was a dose-finding, single-arm trial in which patients with HER2-expressing mCRC who had progressed on 2 or more previous regimens received 6.4 mg/kg of intravenous trastuzumab deruxtecan every 3 weeks. Patients were enrolled into 3 cohorts based on HER2 expression level by immunohistochemistry (IHC).

The results showed that trastuzumab deruxtecan elicited an overall response rate of 45.3% in cohort A, which comprised patients with HER2-positive tumors. The median duration of response was 7 months, and the median progression-free survival was 6.9 months in this cohort.

DESTINY-CRC02 is further evaluating trastuzumab deruxtecan at 5.4 mg/kg and 6.4 mg/kg doses in patients with HER2-overexpressing, RAS wild-type or mutant mCRC, Raghav concludes.