Abstract

8548 Background: Dato-DXd consists of a humanized anti-TROP2 IgG1 mAb conjugated to a potent topoisomerase I inhibitor via a stable cleavable linker. In the Phase 3 TROPION-Lung01 study, Dato-DXd demonstrated a statistically significant improvement in progression-free survival (PFS) over docetaxel in pts with previously treated, locally advanced or metastatic NSCLC (Ahn et al, ESMO 2023). The Phase 1/2, multicenter, open-label, multiple cohort TROPION-PanTumor02 study (NCT05460273) was designed to assess Dato-DXd in Chinese pts with advanced or metastatic solid tumors. Here we present results from the NSCLC cohort. Methods: Chinese pts (aged ≥18 years) with locally advanced or metastatic NSCLC with or without actionable genomic alterations (AGAs), who had been previously treated with immunotherapy and platinum-based chemotherapy (pts without AGAs) or targeted therapy and platinum-based chemotherapy (pts with AGAs), were enrolled. Pts received Dato-DXd (6 mg/kg IV Q3W). The primary endpoint was confirmed objective response rate (ORR) by independent central review (ICR) per RECIST v1.1. Analyses presented are based on the primary analysis data cut-off (DCO; Oct 9, 2023) with 6 months (mos) follow-up post the last pt’s first dose. Results: In the NSCLC cohort, 40 pts from 11 sites in China were enrolled. Median age was 59 years (range 33–74); 29 pts (72.5%) were male, and 18 (45.0%) were current or former smokers. 23 (57.5%)/17 (42.5%) pts had tumors with non-squamous/squamous histology. 5 pts (12.5%) had NSCLC with AGAs; 4 of these pts had sensitizing EGFR mutations. At DCO, 8 pts were ongoing treatment; median study follow-up was 8.1 mos (range 1.1–11.9). Overall, confirmed ORR by ICR was 45.0% (all partial responses), disease control rate by ICR was 85.0%, median duration of confirmed response was 8.3 mos, and median time to onset of response from first dose was 1.4 mos. ORR by ICR was 56.5% (13/23) in the non-squamous subgroup, 29.4% (5/17) in the squamous subgroup, and 75.0% (3/4) in pts with EGFR mutations. Median PFS by ICR (95% CI) was 7.4 mos (5.7–not calculable [NC]) overall, 9.6 mos (7.1–NC) in the non-squamous subgroup, and 5.5 mos (1.4–NC) in the squamous subgroup. Median treatment duration was 5.6 mos (range 0.7–10.6). Treatment-emergent adverse events (TEAEs) occurred in 95.0% of pts; grade ≥3 TEAEs occurred in 57.5%, and there were no fatal TEAEs. The most common TEAEs were nausea (62.5%), stomatitis (57.5%) and anemia (57.5%). TEAEs led to dose reduction/discontinuation in 20.0%/10.0% of pts. No adjudicated drug-related interstitial lung disease was reported. Conclusions: Dato-DXd showed encouraging efficacy in Chinese pts with advanced or metastatic NSCLC; the non-squamous subgroup appeared to derive the most benefit. The efficacy/safety profile was consistent with previous studies, with no new safety signals observed. Clinical trial information: NCT05460273 .