ICARUS-Lung01 Study Evaluates Datopotamab Deruxtecan in Advanced NSCLC

Datopotamab deruxtecan can improve survival in patients with advanced non-small cell lung cancer (NSCLC), specifically in those with non-squamous disease, according to results of the ICARUS-Lung01 study.

Researchers in France investigated the efficacy and safety of the antibody-drug conjugate in a heavily pretreated population of patients. “Few treatments with limited benefit are currently available after failure of targeted therapies, immunotherapy and platinum-based chemotherapy in patients with advanced NSCLC,” the researchers said.

The single-arm, phase 2 study’s primary endpoint was investigator-assessed confirmed objective response rate (ORR). Furthermore, biomarkers associated with response/resistance were determined by a set of translational analyses, including TROP2 tumor membrane expression, TROP2 dynamics and spatial distribution, genomics, transcriptomic, spatial proteomics, and circulating tumor cells.

Most of the patients enrolled in the clinical trial were men (62%), people who smoked (89%), and had non-squamous histology (82%) with a history of at least 2 lines of prior therapy. The median age was 60 years and 23% had actionable genetic alterations. All had an ECOG performance status of 0 or 1.

Intravenous datopotamab deruxtecan 6 mg/kg was given every 21 days to 100 patients with NSCLC who had progressed on 1-3 lines of therapy. Fresh tumor tissue biopsies were conducted in all patients at baseline, during treatment (week 3 or 6), and at the end of treatment. The median treatment duration was 2.8 months (95% CI, 2.1-4.8) and the median follow-up was 19.4 months (95% CI, 18.2-20.4).

At cut-off, 92% discontinued therapy, 92% had a disease event, and 67% died. These findings were presented by researchers during the 2024 American Society of Clinical Oncology Annual Meeting held May 31-June 4 in Chicago, Illinois.

The researchers observed a confirmed ORR of 28% (non-squamous [32.9%] vs squamous [5%]. Moreover, the datopotamab deruxtecan improved survival in patients with the disease. Median overall survival (OS) was 11.9 months. Patients with non-squamous disease had an OS of 12.6 months and squamous was 6.3 months. The median progression-free survival (PFS) rate was 3.6 months (non-squamous 4.8 months vs squamous 2.9 months). The disease control rate was 75%.

Twenty-five percent of patients experienced a grade 3 treatment-related adverse event (TRAE). The 2 most common TRAEs were stomatitis (49%) and nausea (45%). The researchers noted 1 confirmed case of interstitial lung disease.

“In this heavily pretreated population, [datopotamab deruxtecan] showed similar efficacy and safety results to those reported in TROPION-Lung01,” the researchers said. “Patients with non-squamous (disease) appeared to derive the greatest benefit.”

Reference

Planchard D, Cozic N, Wislez M, et al. ICARUS-LUNG01: A phase 2 study of datopotomab deruxtecan (Dato-DXd) in patients with previously treated advanced non-small cell lung cancer (NSCLC), with sequential tissue biopsies and biomarkers analysis to predict treatment outcome. Abstract #8501. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024, Chicago, Illinois.