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

Author(s): Jacob Sands, MD¹; Myung-Ju Ahn, MD¹; Aaron Lisberg, MD^1,2; Byoung Chul Cho, MD, PhD^1,3; George Blumenschein Jr, MD^1,4; Elaine Shum, MD^1,5; Elvire Pons Tostivint, MD, PhD^1,6; Yasushi Goto, MD, PhD^1,7; Kiyotaka Yoh, MD⁸; Rebecca Heist, MD, MPH⁹; Junichi Shimizu, MD, PhD¹⁰; Jong-Seok Lee, MD, PhD¹¹; Paul Baas, MD, PhD^1,12; David Planchard, MD, PhD^1,13,14; Maurice Pérol, MD^1,15; Enriqueta Felip, MD, PhD^1,16; Wu-Chou Su, MD^1,17; Hong Zebger-Gong, MD, PhD¹⁸; Lan Lan, PhD¹⁹; Chelsea Liu, PhD¹⁹; Paul Howarth, MD¹⁹; Rachel Chiaverelli, PhD¹⁹; Luis Paz-Ares, MD, PhD^1,20

Source: https://doi.org/10.1200/JCO-24-01349

Dr. Maen Hussein's Thoughts

Dato showed a confirmed overall response rate (ORR) of 42.7% with a complete response (CR) of 4.3%. The median duration of response was 7.0 months, with a disease control rate of 86.3% and a median overall survival (OS) of 15.6 months. This could be another option for EGFR mutant patients who had multiple lines of therapy.

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 METHODS

Patients received Dato-DXd 6 mg/kg once every 3 weeks. The primary end point 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.

Author Affiliations

¹Dana-Farber Cancer Institute, Boston, MA;²David Geffen School of Medicine at UCLA, Los Angeles, CA;³Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea;⁴The University of Texas MD Anderson Cancer Center, Houston, TX;⁵NYU Langone Health Perlmutter Cancer Center, New York, NY;⁶University Hospital of Nantes, Nantes, France;⁷National Cancer Center Hospital, Tokyo, Japan;⁸National Cancer Center Hospital East, Kashiwa, Japan;⁹Massachusetts General Hospital Cancer Center, Harvard Medical School, Harvard University, Boston, MA;¹⁰Aichi Cancer Center Hospital, Aichi, Japan;¹¹Seoul National University Bundang Hospital, Seongnam, Republic of Korea;¹²The Netherlands Cancer Institute, The Leiden University Medical Center, Amsterdam, the Netherlands;¹³Gustave Roussy, Department of Medical Oncology, Thoracic Group, Villejuif, France;¹⁴Paris-Saclay University, Paris, France;¹⁵Centre Léon Bérard, Lyon, France;¹⁶Vall d’Hebron Hospital Campus, Vall d’Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain;¹⁷National Cheng Kung University Hospital, Tainan, Taiwan;¹⁸Daiichi Sankyo Europe GmbH, Munich, Germany;¹⁹Daiichi Sankyo, Inc, Basking Ridge, NJ;²⁰Hospital Universitario 12 de Octubre, CNIO-H120 Lung Cancer Unit, Complutense University and Cibereronc, Madrid, Spain

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