Dato-DXd vs Docetaxel in Previously Treated Advanced/Metastatic Non–Small Cell Lung Cancer: Results of the Randomized Phase III Study TROPION-Lung01

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.

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.

Ahn M, Lisberg AE, Paz-Ares L et al. LBA12 - 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. Abstract presented at: ESMO Congress 2023, October 20-24, 2023.