KEY TAKEAWAYS
- The TROPION-LUNG01 phase III trial aimed to evaluate whether Dato-DXd improves PFS compared to DTX in pre-treated advanced/metastatic NSCLC patients, regardless of AGA status.
- The results demonstrated improved PFS over docetaxel in pretreated advanced/metastatic NSCLC, with manageable safety.
Dato-DXd is an innovative antibody-drug conjugate targeting TROP2, currently undergoing clinical investigation across various tumor types.
Myung-Ju Ahn and her team aimed to present the initial findings from TROPION-Lung01 (NCT04656652), a global phase 3 study, comparing Dato-DXd with docetaxel in previously treated patients with advanced/metastatic NSCLC, irrespective of actionable genomic alterations.
Patients were randomly assigned in a 1:1 ratio to receive either Dato-DXd at 6 mg/kg or docetaxel (DTX) at 75 mg/m2 every 3 weeks (Q3W). The study’s primary endpoints were progression-free survival (PFS), evaluated by blinded independent central review (BICR), and overall survival (OS). Secondary endpoints included objective response rate (ORR), duration of response (DOR), and safety assessments.
In the full analysis set (FAS) of 604 patients (43.1% with ≥2 prior lines of therapy; median age 64 years), Dato-DXd demonstrated significantly improved PFS compared to docetaxel (HR, 0.75; 95% CI, 0.62-0.91; P=.004; median, 4.4 vs. 3.7 months). Confirmed ORR were 26.4% (Dato-DXd) and 12.8% (DTX), with median durations of response of 7.1 and 5.6 months, respectively. Subgroup analyses revealed longer median PFS in non-squamous histology (NSQ; 5.6 vs. 3.7 months) and actionable genomic alterations (AGA; 6.8 vs. 2.6 months). Median treatment durations were 4.2 months (range, 0.7-18.3 months) for Dato-DXd and 2.8 months (range, 0.7-18.9 months) for DTX.
Common treatment-emergent adverse events (TEAEs) with Dato-DXd included stomatitis (49.2%, mostly grade [gr] 1/2) and nausea (37%). Adjudicated drug-related interstitial lung disease gr ≥3 occurred in 3.4% of patients with Dato-DXd vs. 1.4% with DTX. Dato-DXd exhibited fewer drug-related gr ≥3 TEAEs and adverse events leading to dose reduction or discontinuation compared to DTX.
The study showcased significantly improved PFS over DTX, benefiting non-squamous histology and those with actionable genomic alterations. Dato-DXd exhibited a well-tolerated and manageable safety profile, with the trial ongoing until the final OS analysis. The research was sponsored by Daiichi Sankyo, Inc.
Source: https://cslide.ctimeetingtech.com/asia2023/attendee/confcal/show/session/36
Clinical Trial: https://clinicaltrials.gov/study/NCT04656652
Ahn MJ et al. “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.’’ Presented at ESMO Asia Congress 2023. (Presentation Number 509MO).
