LBA49 Efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC) and actionable genomic alterations (AGAs): Preliminary results from the phase I TROPION-PanTumor01 study

Pts with adv/met NSCLC with AGAs derive limited benefit from existing treatments once tyrosine kinase inhibitors (TKIs) and platinum chemotherapies fail. Dato-DXd is an antibody-drug conjugate comprising a TROP2-directed monoclonal antibody conjugated to a potent topoisomerase I inhibitor via a stable tetrapeptide-based cleavable linker. Dato-DXd showed encouraging antitumor activity in the phase 1 TROPION-PanTumor01 trial in heavily pretreated pts with adv/met NSCLC treated with 4, 6, and 8 mg/kg. Here, we report results from this trial for pts with NSCLC with AGAs. TROPION-PanTumor01 (NCT03401385) is an ongoing multicenter, open-label, dose-expansion study evaluating Dato-DXd in solid tumors, including NSCLC in 210 pts. It is assessing safety, pharmacokinetics, antitumor activity, and biomarkers in pts who progressed after standard treatment or had no standard treatment available and had measurable disease. Stable/treated brain metastases were permitted. Pts were not selected based on TROP2 expression or AGA status. 34 pts had adv/met NSCLC with AGAs (8 at 4 mg/kg, 10 at 6 mg/kg, and 16 at 8 mg/kg). Median age was 62 years; 56% were women and 44% were men. Investigator-reported AGAs were EGFR (n=29), ALK (n=3), and ROS1 and RET (both n=1). 82% of pts received ≥3 prior regimens and 85% prior TKI; 69% of pts with EGFR mutations had prior osimertinib. Median duration on study was 13 months. Confirmed ORR by BICR across doses was 35% (95% CI, 19.7-53.5). Median DOR was 9.5 months (95% CI, 3.3-NE). Most common any-grade AEs were nausea (62%) and stomatitis (56%); hematologic toxicities were infrequent. There was 1 incidence of treatment-related adjudicated interstitial lung disease, a grade 5 event at 8 mg/kg. Antitumor activity and safety in adv/met NSCLC pts with AGAs are encouraging. The ongoing phase 2 TROPION-Lung05 trial (NCT04484142) is assessing Dato-DXd at 6 mg/kg in adv/met NSCLC with AGAs after targeted therapies and platinum chemotherapy.