Datopotamab Deruxtecan in Advanced or Metastatic Non–Small Cell Lung Cancer With Actionable Genomic Alterations Results From the Phase II TROPION-Lung05 Study

Jacob Sands, Myung Ju Ahn, Aaron Lisberg, Byoung Chul Cho, George Blumenschein, Elaine Shum, Elvire Pons Tostivint, Yasushi Goto, Kiyotaka Yoh, Rebecca Heist, Junichi Shimizu, Jong Seok Lee, Paul Baas, David Planchard, Maurice Pérol, Enriqueta Felip, Wu Chou Su, Hong Zebger-Gong, Lan Lan, Chelsea LiuPaul Howarth, Rachel Chiaverelli, Luis Paz-Ares

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    Résumé

    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.

    langue originaleAnglais
    Numéro d'article1349
    journalJournal of Clinical Oncology
    Les DOIs
    étatAccepté/sous presse - 1 janv. 2025

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