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 

 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.

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Natalie Vokes, MD, discusses emerging biomarkers in non–small cell lung cancer, specifically highlighting the promise of HER3-targeted therapy.


Dr Vokes on Targeting HER3 in NSCLC

Natalie I. U. Vokes, MD, a medical oncologist fellow at Dana-Farber Cancer Institute, discusses investigative biomarkers of response to checkpoint inhibitors in the field of oncology.

Tumor mutational burden is the most well-developed biomarker in the field of oncology, says Vokes. Many of the early studies that used whole exome sequencing and looked for genomic correlates noted that TMB in patients who responded to treatment is often higher than in those who do not respond. 

This was initially demonstrated in studies that used whole exome sequencing in melanoma and has since been confirmed via a number of different sequencing techniques in an array of disease contexts. There has been a lot of interest in further developing TMB as a biomarker. 

Other biomarkers are not as well developed, adds Vokes. For example, in lung cancer, 1 biomarker that comes up quite a bit are 

 mutations; this is generally a poor prognostic marker across different treatment settings, Vokes adds. There is also some work showing the presence or absence of other comutations, such as 

 mutation is. There is a lot that the field still has to learn in that regard, says Vokes.

In lung cancer, the use of driver mutations as biomarkers, such as 

, are taken for granted, she adds. Those patients tend to not respond as well to treatment, but 1 should be cautious that this is not extended to all driver alterations in non–small cell lung cancer. This is because mutations such as 

 might be biologically different. The field is still learning about these other biomarkers and stronger understanding is anticipated over the next couple of years, concludes Vokes.

Natalie I. U. Vokes, MD, discusses investigative biomarkers of response to checkpoint inhibitors in the field of oncology.

Natalie I. U. Vokes, MD

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Dr Vokes on Targeting HER3 in NSCLC

Dr. Vokes on Investigative Biomarkers of Response to Checkpoint Inhibitors in Cancer