Intracranial efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously treated advanced/metastatic non-small cell lung cancer (a/m NSCLC) with actionable genomic alterations (AGA): Results from TROPION-Lung05.

• DOI: 10.1200/jco.2024.42.16_suppl.8593
• Publication Date: 2024-06-26T16:58:54Z
• Authors: Aaron Lisberg; Myung-Ju Ahn; Satoru Kitazono; Byoung Chul Cho; George R. Blumens...; Elaine Shum; Elvire Pons-Tosti...; Yasushi Goto; Kiyotaka Yoh; Luis G. Paz-Ares; Rebecca Suk Heist; Paul Baas; David Planchard; Maurice Perol; Enriqueta Felip; Wu-Chou Su; Hong Zebger-Gong; Lan Lan; Chelsea Liu; Jacob Sands
• Keywords: 03 medical and health sciences; 0302 clinical medicine

8593 Background: Brain metastases (mets) occur frequently in pts with NSCLC, particularly certain AGAs, and indicate poor prognosis. For treatment options are limited once targeted therapy platinum-based chemotherapy (Pt-CT) become ineffective. The phase 2 TROPION-Lung05 trial (NCT04484142) of Dato-DXd has demonstrated systemic efficacy a manageable safety profile heavily pretreated a/m NSCLC AGAs who progressed following Pt-CT; here we report an exploratory analysis intracranial (IC) efficacy. Methods: Pts were treated 6 mg/kg IV Q3W. clinically stable brain mets eligible. IC responses assessed by blinded independent central review (BICR) cranial CT/MRI (CNS BICR; per CNS RECIST) at baseline (BL) Q6W. Systemic objective response rate (ORR), disease control (DCR), clinical benefit (CBR, defined as CR+PR+SD or non-CR/non-PD lasting ≥6 mo), progression-free survival (PFS) BICR RECIST 1.1 treatment-related adverse events (TRAEs) determined without BL mets. Results: In total 53/137 (39%) had mets; 29/53 (55%) EGFRmutation. median (range) 3 (2–6) prior therapies the setting, including Pt-CT with/without immune checkpoint inhibitors; 15/53 (28%) untreated At data cutoff (Dec 14, 2022), study durations among 14.8 (9.7–20.5) 3.2 (0.7–17.2) mo, respectively. Of these pts, 18/53 (34%) measurable target lesions (3 untreated) 35/53 (66%) only non-target lesions. 18 lesions, ORR was 22% (95% CI, 6–48), 1 lesions; DCR 72% 47–90); CBR 44% 22–69). Reduction sum diameters seen 10/18 (56%). Median time to 1.5 (range, 1.3–5.4) mo; duration 5.5 3.4–NE) mo similar (Table). Conclusions: showed encouraging activity consistent supporting further investigation Clinical information: NCT04484142 . [Table: see text]