Talking HER2-Targeted Therapy With Dr. Ajani

Welcome to a very special series with OncLive! I’m your host today, Caroline Seymour.

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We had the pleasure of speaking with Jaffer Ajani, MD, professor of medicine, and internist in the Department of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, who discussed some of the investigational HER2-targeted treatment strategies with trastuzumab, antibody-drug conjugates, and bispecific antibodies that are under investigation in gastrointestinal malignancies.

Several clinical trials are ongoing in gastric cancer and colorectal cancer and through this research, investigators are seeking to define the optimal HER2-targeted approach, explained Ajani. For example, in the phase III KEYNOTE-811 trial, previously untreated patients with advanced HER2-positive gastric/gastroesophageal cancer will be randomized to receive the combination of trastuzumab and chemotherapy plus pembrolizumab or placebo.

Additionally, in an ongoing phase II trial, investigators are evaluating the safety and efficacy of combining the bispecific antibody ZW25 with physician’s choice of chemotherapy in patients with previously untreated, advanced HER2-positive GEJ cancer.

Following encouraging data with the ADC DS-8201a in patients with unresectable or metastatic HER2-positive gastric/GEJ cancer who had received at least 2 prior therapies, the drug is being evaluated as second-line therapy in patients with unresectable or metastatic disease in the phase II DESTINY-Gastric02 trial.

Moreover, the monoclonal antibody margetuximab is under evaluation as frontline therapy in the multiarm phase II/III MAHOGANY trial in combination with PD-1 and anti—LAG-3 inhibition in patients with HER2-positive gastric/GEJ cancer.

In colorectal cancer, DS-8201a and ZW25 have shown the most potential, said Ajani; however, where these agents will play a role in the treatment landscape has yet to be determined.

Listen on to hear Ajani discuss some of the HER2-targeted strategies that are under exploration in gastric/GEJ cancer and colorectal cancer, the potential downsides of bulk tumor testing, and the promise of liquid biopsies in the space.