TY - JOUR
T1 - Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations Results From the Phase II TROPION-Lung05 Study
AU - Sands, Jacob
AU - Ahn, Myung Ju
AU - Lisberg, Aaron
AU - Cho, Byoung Chul
AU - Blumenschein, George
AU - Shum, Elaine
AU - Tostivint, Elvire Pons
AU - Goto, Yasushi
AU - Yoh, Kiyotaka
AU - Heist, Rebecca
AU - Shimizu, Junichi
AU - Lee, Jong Seok
AU - Baas, Paul
AU - Planchard, David
AU - Pérol, Maurice
AU - Felip, Enriqueta
AU - Su, Wu Chou
AU - Zebger-Gong, Hong
AU - Lan, Lan
AU - Liu, Chelsea
AU - Howarth, Paul
AU - Chiaverelli, Rachel
AU - Paz-Ares, Luis
N1 - Publisher Copyright:
© 2025 by American Society of Clinical Oncology.
PY - 2025/1/1
Y1 - 2025/1/1
N2 - PURPOSE Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2–directed antibody-drug conjugate with a highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier: NCT04484142) evaluated the safety and clinical activity of Dato-DXd in patients with advanced/metastatic non–small cell lung cancer (NSCLC) with actionable genomic alterations progressing on or after targeted therapy and platinum-based chemotherapy. PATIENTS AND Patients received Dato-DXd 6 mg/kg once every 3 weeks. The primary end point METHODS was objective response rate (ORR) by blinded independent central review. Secondary end points included duration of response (DOR), safety, tolerability, and survival. RESULTS Among 137 patients who received at least 1 dose of Dato-DXd, 71.5% received at least three lines of prior therapies for advanced/metastatic disease. Overall, 56.9% had EGFR mutations and 24.8% had ALK rearrangements. Median treatment duration was 4.4 months (range, 0.7-20.6). The confirmed ORR was 35.8% (95% CI, 27.8 to 44.4) overall, and 43.6% (95% CI, 32.4 to 55.3) and 23.5% (95% CI, 10.7 to 41.2) in those with EGFR mutations and ALK rearrangements, respectively. The median DOR was 7.0 months (95% CI, 4.2 to 9.8), and the overall disease control rate was 78.8% (95% CI, 71.0 to 85.3). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 28.5% of patients. The most common TRAE was stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) patients experienced adjudicated treatment-related interstitial lung disease/pneumonitis, with 1 (0.7%) grade 5 event. CONCLUSION Encouraging and durable antitumor activity was observed with Dato-DXd in this heavily pretreated advanced/metastatic NSCLC population with actionable genomic alterations. The rate of treatment-related grade ≥3 toxicities was comparable with previous observations, and no new safety signals were observed.
AB - PURPOSE Datopotamab deruxtecan (Dato-DXd) is a trophoblast cell-surface antigen-2–directed antibody-drug conjugate with a highly potent topoisomerase I inhibitor payload. The TROPION-Lung05 phase II trial (ClinicalTrials.gov identifier: NCT04484142) evaluated the safety and clinical activity of Dato-DXd in patients with advanced/metastatic non–small cell lung cancer (NSCLC) with actionable genomic alterations progressing on or after targeted therapy and platinum-based chemotherapy. PATIENTS AND Patients received Dato-DXd 6 mg/kg once every 3 weeks. The primary end point METHODS was objective response rate (ORR) by blinded independent central review. Secondary end points included duration of response (DOR), safety, tolerability, and survival. RESULTS Among 137 patients who received at least 1 dose of Dato-DXd, 71.5% received at least three lines of prior therapies for advanced/metastatic disease. Overall, 56.9% had EGFR mutations and 24.8% had ALK rearrangements. Median treatment duration was 4.4 months (range, 0.7-20.6). The confirmed ORR was 35.8% (95% CI, 27.8 to 44.4) overall, and 43.6% (95% CI, 32.4 to 55.3) and 23.5% (95% CI, 10.7 to 41.2) in those with EGFR mutations and ALK rearrangements, respectively. The median DOR was 7.0 months (95% CI, 4.2 to 9.8), and the overall disease control rate was 78.8% (95% CI, 71.0 to 85.3). Grade ≥3 treatment-related adverse events (TRAEs) occurred in 28.5% of patients. The most common TRAE was stomatitis (preferred term; any grade: 56.2%; grade ≥3: 9.5%). Five (3.6%) patients experienced adjudicated treatment-related interstitial lung disease/pneumonitis, with 1 (0.7%) grade 5 event. CONCLUSION Encouraging and durable antitumor activity was observed with Dato-DXd in this heavily pretreated advanced/metastatic NSCLC population with actionable genomic alterations. The rate of treatment-related grade ≥3 toxicities was comparable with previous observations, and no new safety signals were observed.
UR - http://www.scopus.com/inward/record.url?scp=85215581055&partnerID=8YFLogxK
U2 - 10.1200/JCO-24-01349
DO - 10.1200/JCO-24-01349
M3 - Article
AN - SCOPUS:85215581055
SN - 0732-183X
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
M1 - 1349
ER -