Lyudmila A. Bazhenova, MD, on ROS1-Positive NSCLC: Taletrectinib in TKI-Naive Patients
AACR 2026
Lyudmila A. Bazhenova, MD, of the University of California, San Diego, presents updated data from the phase II TRUST-I and TRUST-II trials. With approximately 3 years of follow-up in the pooled analysis, investigators now conclude that the next-generation, selective ROS1 tyrosine kinase inhibitor (TKI) is an effective and tolerable treatment option for patients with advanced ROS1 mutation–positive NSCLC who have not received a prior ROS1 TKI (Abstract CT300).
Yuji Shibata, MD, PhD, of The University of Texas MD Anderson Cancer Center, describes findings on the identification of novel HER2 mutations that mediate resistance to the tyrosine kinase inhibitor zongertinib among patients with non–small cell lung cancer (NSCLC); these data also indicated that sevabertinib may be effective against a subset of these genomic alterations (Abstract 7025).
Melissa Johnson, MD, of Sarah Cannon Research Institute, reviews results from a cohort of the phase I ARTEMIS-101 trial, which she was the discussant of at AACR 2026. The subgroup of cohort 1a included patients with advanced nonsquamous non–small cell lung cancer and no actionable genomic alterations. The combination of the novel antibody-drug conjugate risvutatug rezetecan and the monoclonal antibody adebrelimab showed a “trend towards improved efficacy” vs monotherapy with risvutatug rezetecan in this patient population (Abstract CT038).
Thi Van Trinh Tran, PhD, of the National Cancer Institute, describes histologic and prognostic findings from the largest cohort of lung cancer in people who have never smoked. Tumor-infiltrating lymphocyte data also reflected refined risk stratification (Abstract 1302).
Jonathan Riess, MD, of the University of California, Davis, describes preliminary data on the safety and clinical activity of zoldonrasib (also known as RMC-9805), an oral, RAS(ON) G12D–selective, tricomplex inhibitor, in previously treated patients with KRAS G12D–mutant non–small cell lung cancer (NSCLC) (Abstract CT021).
Manale El Kharbili, PhD, of the University of Colorado Anschutz Medical Campus, discusses preclinical work that showed HER2-mutant non–small cell lung cancer (NSCLC) cell lines retained demonstrated dynamic changes in cell surface protein expression in treatment-naive vs zongertinib-induced measurable residual disease (MRD) states. Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant HER2-driven lines demonstrated high sensitivity to therapies targeting surface proteins, which correlated with their level of expression—representing a potential novel therapeutic strategy for eradicating MRD and preventing relapse in these patients (Abstract 3166).
