Dr Kim on the Importance of the FDA Approval of Repotrectinib for ROS1+ NSCLC

Chul Kim, MD, MPH, thoracic oncologist, associate professor, medical oncology, Georgetown University Lombardi Comprehensive Cancer Center, MedStar Health, discusses the impact of optimizing rare targets in non–small cell lung cancer (NSCLC), such as ROS1 and ALK, highlighting the FDA approval of repotrectinib (Augtyro) in ROS1-positive disease.

Previously, the NSCLC treatment armamentarium included 2 ROS1 TKIs: crizotinib (Xalkori) and entrectinib (Rozlytrek), Kim begins. On November 15, 2023, the FDA approved repotrectinib for patients with locally advanced or metastatic ROS1-positive NSCLC, heralding the advent of a new generation of ROS1 TKIs, he emphasizes. In the first-line phase 1/2 TRIDENT-1 trial (NCT03093116), repotrectinib elicited a response rate of 79% (95% CI, 68%-88%) coupled with a median duration of response (DOR) of 34.1 months. Conversely, in patients pretreated with ROS1 TKIs, the response rate was 38% (95% CI, 25%-52%), with a median DOR of 14.8 months, he explains. Repotrectinib showcased activity in a substantial subset of patients who experienced disease progression on prior ROS1 TKI therapy, even overcoming resistance mechanisms such as G2032R, Kim states.

Notably, repotrectinib targets ROS1 and the TRK pathway. Consequently, it becomes imperative to monitor adverse events (AEs) related to TRK inhibition, he expands. Neurological AEs, including dizziness, altered taste, neuropathy, and ataxia, are occasionally observed in association with TRK inhibition. Additionally, vigilant monitoring for other AEs, such as weight gain and withdrawal pain, is warranted, Kim says.

Antibody-drug conjugates (ADCs) represent a burgeoning field in thoracic oncology and oncology at large, he continues. Among these, fam-trastuzumab deruxtecan-nxki (Enhertu), a HER2-directed ADC, has garnered approval for patients with HER2-positive NSCLC, Kim explains, adding that numerous ADCs are in development for various indications, targeting diverse entities such as TROP2, MET, and others.

Kim emphasizes that telisotuzumab vedotin (Teliso-V), a MET-directed ADC, exhibited an objective response rate of 36.5% (95% CI, 23.6%-51.0%) in patients with c-Met–high NSCLC in the phase 2 LUMINOSITY trial (NCT03539536). Currently, the randomized phase 3 TeliMET NSCLC-01 trial (NCT04928846) is underway to compare telisotuzumab vedotin with docetaxel, and the trial's final outcomes are eagerly awaited, he concludes.