First-line (1L) datopotamab deruxtecan (Dato-DXd) + rilvegostomig in advanced or metastatic non-small cell lung cancer (a/mNSCLC): Results from TROPION-Lung04 (cohort 5).

作者：Saiama N. Waqar, Kristof Cuppens, Rosario García Campelo, Rafał Dziadziuszko, Enric Carcereny, Tsung‐Ying Yang, Jin‐Yuan Shih, Giselle Dutcher, Silvia Novello, Izabela Chmielewska, Ewa Kalinka‐Warzocha, Mehmet Ali Nahit Sendur, Kazushige Wakuda, Alexandra Tyulyandina, Mateusz Hinzmann, Xiaojin Shi, Shankar Bodla, Kyriakos P. Papadopoulos · 发表于：Journal of Clinical Oncology · 年份：2025 · DOI：10.1200/jco.2025.43.16_suppl.8521 · 被引用次数：10 · 研究领域：Lung Cancer Treatments and Mutations、Lung Cancer Research Studies、Chemical Reactions and Isotopes

8521 Background: 1L anti–PD-(L)1 antibodies ± chemotherapy are standard of care for patients (pts) with a/mNSCLC without actionable genomic alterations (AGAs). However, not all pts experience response to treatment. Dato-DXd, a TROP2-directed antibody-drug conjugate, has shown efficacy in pts with a/mNSCLC alone or combined with PD-(L)1 inhibitors. Rilvegostomig, a bispecific antibody targeting PD-1 and TIGIT, has also shown preliminary efficacy in pts with a/mNSCLC. Consequently, the combination of Dato-DXd and rilvegostomig may have the potential to enhance responses. Methods: TROPION-Lung04 (NCT04612751) is a phase 1b, open-label, dose-escalation and expansion study enrolling pts with a/mNSCLC without AGAs. In cohort 5 (C5; C5a, PD-L1 tumor proportion score [TPS] ≥50% and C5b, PD-L1 TPS <50%) treatment-naïve pts received Dato-DXd (6 mg/kg) + rilvegostomig IV Q3W. Pts were treated until disease progression or unacceptable toxicity. The primary endpoint was safety. Secondary endpoints included objective response rate (ORR), duration of response (DoR) and progression-free survival (PFS) per investigator (RECIST v1.1). Results: At data cut-off (DCO; 24 Oct, 2024), 40 pts had received Dato-DXd + rilvegostomig (C5a, n=20; C5b, n=20); 29 (72.5%) had non-squamous histology. Median treatment duration was 5.1 months (range 0.7–18.6); 21 pts discontinued Dato-DXd (adverse events [AEs], n=9; progressive disease [PD], n=9), 20 discontinued rilvegostomig (AEs, n=8; PD, n=9) and 20 (50...