Trastuzumab deruxtecan (T-DXd) in patients (pts) with <i>HER2</i> -mutant (HER2m) non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases (mets): Results from DESTINY-Lung05 (DL-05).

e20500 Background: T-DXd (5.4 mg/kg) is approved in multiple countries for pretreated unresectable/metastatic HER2m NSCLC; conditional approval in China was supported by DESTINY-Lung02 (DL-02) and DL-05 results. In DL-02, T-DXd showed encouraging CNS activity in this population. Here, we report a post-hoc analysis of DL-05 assessing T-DXd in pts from China with HER2m NSCLC with/without baseline (BL) CNS mets. Methods: DL-05 (NCT05246514), an open-label, single-arm, Phase 2 study, evaluated T-DXd (5.4 mg/kg Q3W IV) in pts from China with metastatic HER2m NSCLC with disease progression on/after ≥1 prior anticancer therapy. Pts with pretreated asymptomatic / neurologically stable CNS mets were eligible. Brain CT or MRI scans were performed in all pts at BL and study end. Pts with CNS mets had brain scans every 6 weeks from enrollment date to 48 weeks, then every 9 weeks until RECIST 1.1-defined progressive disease. Additional brain scans were carried out as clinically indicated. In pts with/without BL CNS mets, systemic efficacy (confirmed objective response rate [cORR], disease control rate [DCR], duration of response [DOR], and progression-free survival [PFS] by independent central review [ICR] per RECIST 1.1; and overall survival [OS]), CNS-PFS by ICR per CNS-modified RECIST 1.1, and safety were assessed. CNS-cORR, CNS-DCR, and CNS-DOR were evaluated in pts with measurable BL CNS mets. Results: At data cutoff (November 4, 2024), 72 pts had received T-DXd; 30 pts had BL CNS mets, including 10 with CNS-measurable disease. Median (range) duration of follow up for all pts was 20.2 (2–27) months. In pts with and without CNS mets, median (range) treatment duration was 7.6 (0.7–26.9) months and 10.5 (0.7–26.6) months, respectively. Systemic efficacy data and CNS-PFS are in the Table. In pts with measurable CNS mets (n=10), CNS-cORR was 40.0% (95% CI 12.2, 73.8; n=4, one complete response was reported), CNS-DCR was 100% (95% CI 69.2, 100), and median CNS-DOR was not evaluable (NE). Drug-related Grade ≥3 adverse events were reported in 60.0% (n=18) and 52.4% (n=22) of pts with and without CNS mets, respectively. Conclusions: T-DXd showed antitumor activity in pts from China with metastatic HER2m NSCLC with and without BL CNS mets; consistent with previous analyses, promising CNS activity was observed. No new safety signals were reported. Results support T-DXd use in pretreated pts with HER2m NSCLC, including those with CNS mets. Clinical trial information: NCT05246514 . BL CNS mets(n=30) No BL CNS mets(n=42) cORR, % (n)*95% CI 46.7 (14)28.3, 65.7 64.3 (27)48.0, 78.4 DCR, % (n)*95% CI 90.0 (27)73.5, 97.9 92.9 (39)80.5, 98.5 Median DOR, months (95% CI)* 7.1 (5.3, 15.3) 14.0 (5.8, NE) Median PFS, months (95% CI)* 8.0 (5.8, 16.5) 13.0 (7.2, NE) Median CNS-PFS, months (95% CI) 7.8 (5.6, 9.9) NE (NE, NE) Median OS, months (95% CI)* 16.6 (13.3, 21.7) 24.0 (19.9, NE) *Systemic assessment.