59P Datopotamab deruxtecan (Dato-DXd) in patients with previously treated advanced non-small cell lung cancer (NSCLC): Nonsquamous (NSQ) histology in the phase III TROPION-Lung01 trial

The phase III TROPION-Lung01 trial (NCT04656652) evaluated Dato-DXd, a TROP2-directed antibody-drug conjugate, in patients with previously treated advanced NSCLC. The study met its dual primary endpoint of progression-free survival (PFS) in the intent-to-treat population with a significant improvement vs docetaxel (hazard ratio HR 0.75; 95% CI, 0.62-0.91; p = 0.004). Interim overall survival (OS) was not mature nor statistically significant, however favored Dato-DXd. Efficacy was primarily attributed to patients with NSQ histology. We report efficacy and safety in the NSQ subgroup from TROPION-Lung01. Patients were randomized 1:1 to Dato-DXd 6 mg/kg or docetaxel 75 mg/m2 every 3 weeks, and histology was a stratification factor. PFS and OS by histology were prespecified subgroup analyses; NSQ safety analysis was post hoc. PFS and tumor response were assessed per RECIST 1.1 by blinded independent central review (BICR). Among 299 patients randomized to Dato-DXd and 305 randomized to docetaxel, 234 in each arm had NSQ histology. At data cutoff (March 29, 2023) median study follow-up was 12.9 months (Dato-DXd) and 12.7 months (docetaxel). In the NSQ subgroup, improved PFS was seen with Dato-DXd vs docetaxel (HR 95% CI, 0.63 0.51-0.79); median 5.5 vs 3.6 months. Additional efficacy is shown in the table. In the NSQ subgroup, any grade treatment-related adverse events (TRAEs) occurred in 88% of patients in each treatment arm, with Grade ≥3 events in 22% treated with Dato-DXd and 41% treated with docetaxel. TRAEs associated with dose reduction occurred in 21% and 30% of patients, respectively; TRAEs led to discontinuation in 9% and 12% of patients, respectively.Table: 59PEfficacy of Dato-DXd in NSQ NSCLCNSQ NSCLCaDato-DXd (n = 234)Docetaxel (n = 234)PFSb,cMedian (95% CI), mo5.5 (4.3-6.9)3.6 (2.9-4.2)HR (95% CI)0.63 (0.51-0.79)6-month PFS,b % (95% CI)47 (40-53)28 (22-35)OS (interim)cMedian (95% CI), mo13.4 (12.1-16.4)11.4 (10.1-13.8)HR (95% CI)0.79 (0.60-1.02)ORRb, n (%)73 (31)30 (13)(95% CI)(25-38)(9-18)CR4 (2)0PR69 (30)30 (13)Duration of responsecMedian (95% CI), mo7.7 (5.6-11.1)5.6 (5.4-6.0)Disease control rate,d n (%)188 (80)143 (61)(95% CI)(75-85)(55-67)aHistology per case report forms; bPer BICR; cKaplan-Meier method; dCR + PR + stable disease + non-CR/non-PD CR, complete response; PD, progressive disease; PR, partial response Open table in a new tab aHistology per case report forms; bPer BICR; cKaplan-Meier method; dCR + PR + stable disease + non-CR/non-PD CR, complete response; PD, progressive disease; PR, partial response In TROPION-Lung01, Dato-DXd demonstrated clinically meaningful PFS benefit vs docetaxel in the subgroup of patients with NSQ NSCLC. Safety profile was manageable. OS assessment continues to final analysis.