Researchers Report Primary Results of TROPION-Lung05

Targeted therapies and platinum-based chemotherapy may become ineffective in patients with advanced/metastatic non-small cell lung cancer (a/mNSCLC) with actionable genomic alterations (AGAs), leaving them with few available treatments with limited benefits. Datopotamab deruxtecan (DATA-DXd) is an antibody-drug conjugate composed of a trophoblast cell surface antigen 2-directed monoclonal antibody covalently linked to a highly potent cytotoxic payload via a stable, tumor-selective, tetrapeptide-based cleavable linker.

During a presentation at the European Society for Medical Oncology (ESMO) Congress 2023, researchers reported primary results of TROPION-Lung05, a global, open-label, phase 2 trial evaluating Dato-DXd in patients with a/mNSCLC with AGA progression on or after one AGA-specific therapy and platinum-based chemotherapy (NCT04484142).

The primary end point of interest was confirmed objective response rate (cORR) by blinded independent central review (BICR). Secondary end points included duration of response (DOR), disease control rate (DCR) by BICR, and safety. Eligible patients had a/mNSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and one documented AGA in EGFR, ALK, ROS1, NTRK, BRAF, MET exon 14 skipping, or RET. Participants received Dato-DXd 6 mg/kg every 21 days.

The cohort included 137 patients who received one dose of the trial drug. Median age was 61.0 years, 71.5% had three prior lines of therapy for a/mNSCLC, and 56.9% had EGFR mutations. As of December 14, 2022, 85.4% discontinued therapy, 63.5% had disease progression, and 49.6% died. Median duration on the drug was 15.2 months. Median DOR was 7.0 months; cORR was 35.87% and DCR was 78.8%. Patients with EGFR mutations had similar results.

In summary, the researchers said, “Dato-DXd showed encouraging antitumor activity, with a clinically meaningful and durable response, in heavily pretreated patients with NSCLC with AGAs. The safety profile was manageable and consistent with prior safety observed with Data-DXd. These data support inclusion of patients with AGAs in the TROPION-Lung01 study (NCT04656652).”

Source: Paz-Ares L, Ahn M-J, Lisberg AE, et al. TROPION-Lung05: datopotamab deruxtecan (Data-DXd) in previously treated non-small cell lung cancer (NSCLC) with actionable genomic alterations (AGAs). Abstract of a poster presented at the ESMO Congress 2023; October 20-24, 2023; Madrid, Spain. Funding for the study was provided by Daiichi Sankyo, Inc.