Is Stage 4 cancer 100% death?
Background
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).
Methods
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.
Results
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 the prespecified non-squamous histology subgroup (NSQ; 5.6 vs 3.7 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: LBA12
| Efficacy | Dato-DXdN=299 | DTXN=305 | HR (95% CI) |
| Median PFSa (95% CI), mo | |||
| FAS | 4.4 (4.2-5.6) | 3.7 (2.9-4.2) | 0.75 (0.62-0.91); P=.004b |
| NSQ; n=229/232 c | 5.6 (4.4-7.0) | 3.7 (2.9-4.2) | 0.63 (0.51-0.78) |
| Confirmed ORRa (95% CI), % | 26.4 (21.5-31.8) | 12.8 (9.3-17.1) | – |
| Median DOR (95% CI), mo | 7.1 (5.6-10.9) | 5.6 (5.4-8.1) | – |
| Safety, n (%) | Dato-DXd n=297 d | DTX n=290 d | – |
| Related TEAEs | – | ||
| Any grade | 257 (86.5) | 252 (86.9) | |
| Grade ≥3 | 73 (24.6) | 120 (41.4) | |
| Related TEAEs associated with: | |||
| Dose reduction | 58 (19.5) | 85 (29.3) | |
| Discontinuation | 23 (7.7) | 34 (11.7) | |
| Deathe | 3 (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. ePer Investigator; adjudicated data will be presented.
Conclusions
PFS was significantly improved with Dato-DXd over DTX in pts with pretreated adv/met NSCLC. NSQ patients 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. M-J. Ahn and A. Lisberg have equally contributed to the study.
Clinical trial identification
NCT04656652.