Dr Reckamp on the Landscape of Current and Emerging ADCs in NSCLC

Karen L. Reckamp, MD, MS, professor of medicine, director, Division of Medical Oncology and Lung Institute, Cedars-Sinai Medical Center, associate director, Clinical Research, Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, discusses current and emerging antibody-drug conjugates (ADCs) in lung cancer in addition to highlighting the development of patritumab deruxtecan (HER3-DXd) and telisotuzumab vedotin (ABBV-399; Teliso-V).

The body of evidence favoring the use of ADCs in lung cancer continues to expand with the addition of new agents to the landscape, Reckamp begins. The HER2-targeted agent fam-trastuzumab deruxtecan-nxki (Enhertu; T-DXd) is currently the only ADC approved by the FDA for adult patients with unresectable or metastatic, HER2-mutated non-small cell lung cancer (NSCLC) that was previously treated in the first line, Reckamp states.

The agent gained accelerated approval in August, 2022, based on findings from the phase 3 DESTINY-Lung02 study (NCT04644237), in which the confirmed overall response rate with T-DXd was 58% and the median duration of response was 8.7 months, Reckamp reports. T-DXd has been evaluated across multiple trials within lung cancer, and produced consistent response rates across dose levels.

In addition to T-DXd, there are 2 ADCs with breakthrough designation in NSCLC: patritumab deruxtecan (HER3-DXd) and telisotuzumab vedotin (ABBV-399; Teliso-V), Reckamp continues, noting that both agents continue to be investigated.

HER3-DXd was granted breakthrough designation status by the FDA for the treatment of patients with EGFR-mutated NSCLC who developed resistance to EGFR TKIs in December, 2021. The regulatory decision was based on data from the dose escalation portion and 2 expansion cohorts of the phase 1 U31402-A-U102 study (NCT03260491). In this study, the agent produced a confirmed ORR of 39% in the heavily pretreated population, Reckamp notes.

In January, 2022, the FDA granted breakthrough designation to the MET-targeted ADC Teliso-V for patients with advanced or metastatic EGFR wild-type NSCLC showing high levels of c-Met overexpression and disease progression on or after prior platinum-based chemotherapy. The agent has been shown to elicit responses in both patients with high MET expression as well as those with METamplification, Reckamp says.