TROPION-Lung02: Datopotamab deruxtecan (Dato-DXd) plus pembrolizumab (pembro) with or without platinum chemotherapy (Pt-CT) as first-line (1L) therapy for advanced non-small cell lung cancer (aNSCLC).
Benjamin Levy, Luis Paz‐Ares, Chien‐Chung Lin, Scott M. Herbert, Tsung‐Ying Yang, Anthony W. Tolcher, Yanyan Lou, Yoshitaka Zenke, Diego Cortinovis, Enriqueta Felip, Manuel Dómine, Konstantinos Leventakos, Emiliano Calvo, Atsushi Horiike, Edward Pan, Keisuke Matsubara, Xiaoyu Jia, Rachel Chiaverelli, Michael Chisamore, Yasushi Goto
Abstract
8501 Background: TROPION-Lung02 (NCT04526691) evaluated the TROP2-directed antibody-drug conjugate (ADC) Dato-DXd plus pembro combination with or without Pt-CT in aNSCLC. Here we report primary analyses of pts receiving combination therapy in the 1L setting. Methods: Pts across 6 cohorts were dosed with Dato-DXd (4 or 6 mg/kg) plus pembro 200 mg alone (doublet) or with pembro plus Pt-CT (triplet; cisplatin 75 mg/m 2 or carboplatin AUC 5) Q3W. PD-L1 expression (tumor proportion score) was assessed locally by immunohistochemistry (22C3 assay). Primary objectives were safety and tolerability; efficacy was a secondary objective. Results: As of Apr 29, 2024, 96 pts received either the doublet (n=42) or triplet (n=54) combination as 1L therapy; 29% and 15% of pts were ongoing, respectively. Median ages were 65 (doublet) and 64 years (triplet). Median treatment durations were 9.7 and 5.8 months, respectively. Stomatitis (doublet, 57%; triplet, 33%) and nausea (doublet, 42%; triplet, 48%), primarily Gr 1–2, were the most common adverse events (AEs) across both regimens. Treatment related serious AEs occurred in 5 (12%) and 12 (22%) pts in each cohort and no deaths related to study drug were seen. Efficacy outcomes, including by histology, are summarized in the Table. Biomarker analyses, including efficacy by PD-L1 status, will be presented. Conclusions: In this largest data set to date evaluating an ADC combined with an anti-PD-1/L1 agent in the 1L setting, the combination of Dato-DXd plus pembro treatment both with and without Pt-CT elicited durable antitumor activity in pts with aNSCLC. Tolerability of the combinations was as expected, based on known profiles of the individual agents. Clinical trial information: NCT04526691 . All 1L (n=96) 1L, Nonsquamous (n=75) 1L, Squamous (n=21) Response, n (%) Doublet (n=42) Triplet (n=54) Doublet (n=33) Triplet (n=42) Doublet (n=9) Triplet (n=12) Confirmed objective response rate 23 (55) 30 (56) 17 (52) 24 (57) 6 (67) 6 (50) Complete response 1 (2) 2 (4) 1 (3) 2 (5) 0 0 Partial response 22 (52) 28 (52) 16 (49) 22 (52) 6 (67) 6 (50) Stable disease 14 (33) 18 (33) 12 (36) 14 (33) 2 (22) 4 (33) Progressive disease 3 (7) 2 (4) 3 (9) 1 (2) 0 1 (8) Disease control rate a 37 (88) 48 (89) 29 (88) 38 (91) 8 (89) 10 (83) Median duration of response, mo (95% CI) 20.1 (9.7–NE) 13.7 (5.7–NE) 24.9 (9.7–NE) 18.0 (8.0–NE) 12.0 (5.5–NE) 5.5 (4.1–NE) Median PFS, mo (95% CI) 11.2 b (8.2–21.3) 6.8 c (5.5–11.1) 11.2 (6.1–21.3) 10.8 (5.5–17.3) 10.2 (0.4–NE) 6.7 (1.0–8.2) a Proportion of pts with confirmed CR + PR + SD at 12 wks. b.c Median (95% CI) PFS follow-up, mo: b 17.3 (11.3−26.8); c 23.5 (17.3−27.9). mo, months; NE, not evaluable.