The following is a summary of “First-in-Human, Phase I Dose-Escalation and Dose-Expansion Study of Trophoblast Cell-Surface Antigen 2–Directed Antibody-Drug Conjugate Datopotamab Deruxtecan in Non–Small-Cell Lung Cancer: TROPION-PanTumor01,” published in the October 2023 issue of Oncology by Shimizu, et al.
For a clinical study, researchers sought to assess the safety, tolerability, and anti-tumor efficacy of datopotamab deruxtecan (Dato-DXd), a novel antibody-drug conjugate directed against trophoblast cell-surface antigen 2 (TROP2). The study focused on patients with solid tumors, particularly those with advanced non-small-cell lung cancer (NSCLC).
The study enrolled adults with locally advanced or metastatic NSCLC. During the dose-escalation phase, patients received Dato-DXd at doses ranging from 0.27 to 10 mg/kg every three weeks. In the dose-expansion phase, patients received 4, 6, or 8 mg/kg of Dato-DXd every three weeks. The primary endpoints were the assessment of safety and tolerability, while secondary endpoints included evaluating the objective response rate (ORR), patient survival, and pharmacokinetics.
A total of 210 patients received Dato-DXd, with 180 enrolled in the 4-8 mg/kg dose-expansion groups. These patients had undergone a median of three previous lines of therapy. The maximum tolerated dose was 8 mg/kg administered once every three weeks, with the recommended dose for further development being 6 mg/kg given once every three weeks. Among patients who received 6 mg/kg (n = 50), the median duration of the study, including follow-up, was 13.3 months, and the median exposure was 3.5 months. The most common treatment-emergent adverse events (TEAEs) of any grade included nausea (64%), stomatitis (60%), and alopecia (42%). Grade 3 or higher TEAEs and treatment-related AEs were observed in 54% and 26% of patients, respectively. Three out of 50 patients (6%) experienced adjudicated drug-related interstitial lung disease (two grade 2 and one grade 4). The ORR was 26% (95% CI, 14.6 to 40.3), with a median duration of response of 10.5 months. Median progression-free survival and overall survival were 6.9 months (95% CI, 2.7 to 8.8 months) and 11.4 months (95% CI, 7.1 to 20.6 months), respectively. Responses were observed irrespective of TROP2 expression.
The study revealed promising anti-tumor activity and a manageable safety profile for Dato-DXd in heavily treated patients with advanced NSCLC. Further investigations are underway to explore its potential as first-line combination therapy in advanced NSCLC, monotherapy in second-line treatment, and beyond.