Dr. Johnson on Datopotamab Deruxtecan in NSCLC With Actionable Genomic Alterations

Melissa L. Johnson, MD, program director, Lung Cancer Research, lead, Solid Tumor Immune Effector Cellular Therapy Program, Sarah Cannon Research Institute, discusses the emergence of datopotamab deruxtecan in non–small cell lung cancer (NSCLC) with actionable genomic alterations.

During the 2021 ESMO Congress, preliminary findings from the phase 1 TROPION-PanTumor01 trial (NCT03401385) were presented. The results demonstrated a 35% overall response rate and a median duration of response of 9.5 months with the antibody-drug conjugate (ADC) datopotamab deruxtecan in patients with heavily pretreated advanced NSCLC and actionable genomic alterations.

As such, the TROP2-directed ADC is being further evaluated in the ongoing phase 2 TROPION-Lung05 trial (NCT04484142) for patients with NSCLC and actionable genomic alterations, including EGFR, ALK, ROS1, RET, BRAF, NTRK, and MET exon 14 skipping, for whom targeted therapy and platinum-based chemotherapy have been exhausted, Johnson explains.

Datopotamab deruxtecan harnesses a novel mechanism of action that has not been broadly utilized in oncogene-driven NSCLC. Moreover, treating this patient population with such an agent was not thought to be therapeutically relevant until recently, so these data represent an encouraging breakthrough in the NSCLC paradigm, Johnson concludes.