509MO Datopotamab deruxtecan (Dato-DXd) vs docetaxel in previously treated advanced/metastatic (adv/met) non-small cell lung cancer (NSCLC): Results of the randomized phase III study TROPION-Lung01

Dato-DXd is a novel TROP2-directed antibody-drug conjugate under clinical investigation in multiple tumor types. This is the first report of TROPION-Lung01 (NCT04656652), a randomized, global, open-label, phase 3 study of Dato-DXd vs docetaxel (DTX) in pretreated patients (pts) with adv/met NSCLC with or without actionable genomic alterations (AGAs). Pts were randomized 1:1 to Dato-DXd 6 mg/kg or DTX 75 mg/m2 Q3W. Dual primary endpoints were progression-free survival (PFS; by blinded independent central review [BICR]) and overall survival (OS). Secondary endpoints included objective response rate (ORR), duration of response (DOR), and safety. 604 pts were included in the full analysis set (FAS); 43.1% had received ≥2 prior lines of systemic therapy. Median age was 64 y (range, 24-88). PFS was significantly improved with Dato-DXd over DTX in the FAS (HR, 0.75; 95% CI, 0.62-0.91; P=.004; median, 4.4 vs 3.7 mo). Confirmed ORRs were 26.4% (Dato-DXd) and 12.8% (DTX), with median DORs of 7.1 and 5.6 mo. Longer median PFS was observed in prespecified subgroups including non-squamous histology (NSQ; 5.6 vs 3.7 mo) and AGA (6.8 vs 2.6 mo). Median treatment duration was 4.2 mo (range, 0.7-18.3 mo) for Dato-DXd and 2.8 mo (range, 0.7-18.9 mo) for DTX. The most common treatment-emergent adverse events (TEAEs) seen with Dato-DXd were stomatitis (49.2%, mostly grade [gr] 1/2) and nausea (37%). Adjudicated drug-related interstitial lung disease gr ≥3 occurred in 3.4% of pts with Dato-DXd vs 1.4% with DTX. Fewer drug-related gr ≥3 TEAEs and AEs leading to dose reduction or discontinuation were seen with Dato-DXd vs DTX.Table: 509MOEfficacyDato-DXdN=299DTXN=305HR (95% CI)Median PFSa (95% CI), mo FAS4.4 (4.2-5.6)3.7 (2.9-4.2)0.75 (0.62-0.91); P=.004bNSQ n=229/232c5.6 (4.4-7.0)3.7 (2.9-4.2)0.63 (0.51-0.78)AGA n=47/50c6.8 (4.2-8.2)2.6 (1.4-4.2)0.38 (0.22-0.65)Confirmed ORRa (95% CI), %26.4 (21.5-31.8)12.8 (9.3-17.1)–Median DOR (95% CI), mo7.1 (5.6-10.9)5.6 (5.4-8.1)–Safety, n (%)Dato-DXdn=297dDTXn=290d–Related TEAEs– Any grade257 (86.5)252 (86.9) Grade ≥373 (24.6)120 (41.4)Related TEAEs associated with: Dose reduction58 (19.5)85 (29.3) Discontinuation23 (7.7)34 (11.7) Death3 (1.0)2 (0.7)aBy BICR. bPFS P value boundary = .008. cNo. of pts in the Dato-DXd and DTX arms. dNo. of pts treated. Open table in a new tab aBy BICR. bPFS P value boundary = .008. cNo. of pts in the Dato-DXd and DTX arms. dNo. of pts treated. PFS was significantly improved with Dato-DXd over DTX in pts with pretreated adv/met NSCLC. NSQ and AGA subsets appeared to derive the most benefit. Dato-DXd was well tolerated, with a manageable safety profile. The trial is continuing until the final OS analysis.