KEY TAKEAWAYS
- The phase 1b TROPION-Lung04 assessed Dato-DXd + durvalumab ± carboplatin in advanced/mNSCLC.
- The trial’s primary endpoint was safety/tolerability, while the secondary endpoints included ORR and DCR.
- The study suggested that Dato-DXd + durvalumab ± carboplatin demonstrated manageable safety and promising antitumor activity in advanced/mNSCLC.
This phase 1b study enrolled patients (pts) ≥ 18 years old with ECOG PS 0/1 and confirmed advanced or metastatic non-small cell lung cancer (mNSCLC) without actionable genomic alterations received Dato-DXd (4 mg/kg, Cohorts 1/3; 6 mg/kg, Cohorts 2/4) + durvalumab (1120 mg, all cohorts) ± up to 4 cycles of carboplatin (AUC 5, Cohorts 3/4), Q3W until disease progression (RECIST v1.1)/unacceptable toxicity. Part 1 (dose escalation) used a modified toxicity probability interval-2 (mTPI-2) design with 3‒6 pts. Part 2 (dose expansion) followed with the primary endpoint: safety/tolerability. Secondary endpoints included objective response rate (ORR) and disease control rate (DCR).
As of the data cut-off (DCO; 6-March-2023), 38 pts were evaluable across Cohorts 1 (n=5), 2 (n=19), and 4 (n=14). Cohort 1, Part 1 completed with no dose-limiting toxicities (DLTs), leading to the opening of Cohort 2, Part 1. Cohort 3 was skipped, and Cohort 4, Part 1 was opened. Two pts reported DLTs in Cohort 4. Dose expansion occurred in Cohorts 2 (doublet) and 4 (triplet) without further DLTs. Median ages were 63/67 years, and 73.7%/64.3% were male. Most pts were treatment-naïve. PD-L1 expression levels varied. Median treatment cycles were 8.0 (Cohort 2) and 8.5 (Cohort 4).
Treatment-emergent adverse events (TEAEs) occurred, with constipation and stomatitis being common in Cohort 2 and stomatitis and anemia in Cohort 4. TEAEs leading to treatment discontinuations and Dato-DXd dose reductions were observed without treatment-related deaths. In Cohort 2 first-line pts, ORR was 50.0%, and DCR was 92.9%; in Cohort 4 first-line pts, ORR was 76.9%, and DCR was 92.3%. Dato-DXd + durvalumab ± carboplatin demonstrated manageable safety and promising antitumor activity in advanced/mNSCLC.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/2746
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT04612751
Papadopoulos, K.P., Bruno, D., Kitazono, S., Murakami, S., Gutierrez, M., Wakuda, K., Spira, A., Cuppens, K., Lovick, S., Hepner, A., Mak, G., Waqar, S.N. Datopotamab Deruxtecan (Dato-DXd) + Durvalumab ± Carboplatin in Advanced/mNSCLC: Initial Results from Phase 1b TROPION-Lung04.
