Dr Vokes on Targeting HER3 in NSCLC

Natalie Vokes, MD, assistant professor, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses emerging biomarkers in non–small cell lung cancer (NSCLC), specifically highlighting the promise of HER3-targeted therapy.

HER3 has been investigated as a target in NSCLC for a long time, Vokes begins, adding that oncologists have seen the failures of many different antibody inhibitors in patients with NSCLC. However, despite these setbacks, oncologists are starting to see that using HER3 as a target for antibody-drug conjugates (ADCs) is a promising approach, and researchers are beginning to see a bit of traction with HER3 ADCs Vokes explains.

Data presented at the 2021 and 2022 ASCO Annual Meetings showed activity with HER3-directed ADCs, both in the refractory EGFR-positive NSCLC and EGFR wild-type NSCLC populations, Vokes expands. These agents are also moving into further expansion trials and combination trials with TKIs and other agents, making for an exciting future in this treatment arena, she says.

Moreover, HER3-directed ADCs are associated with high response rates and beneficial disease control rates, as well as promising safety profiles, Vokes continues, noting that these drugs appear to be well tolerated. Data from a phase 1 trial (NCT05194982) investigating a HER2-directed bispecific ADC in patients with locally advanced or metastatic solid tumors were presented at the 2023 ASCO Annual meeting, according to Vokes. This continued investigation of HER3 as a target evaluated a HER3/EGFR-targeted ADC with a chemotherapy payload called BL-B01D1, Vokes explains. Treatment with BL-B01D1 produced high response rates and disease control rates in patients with solid tumors including NSCLC and small cell lung cancer, Vokes adds. This research will develop going forward as investigators collect more international data with this agent and observe its effects in greater patient numbers, she concludes.