TROPION-Lung04 Examines New Antibody-Drug Conjugate in Combination Therapy
Posted: Thursday, October 28, 2021
Because preclinical and phase I study results have indicated that datopotamab deruxtecan may prove to be an effective treatment option for patients with advanced or metastatic non–small cell lung cancer (NSCLC), it is being evaluated in a two-part phase Ib trial, TROPION-Lung04, according to Hossein Borghaei, DO, MS, of Fox Chase Cancer Center, Philadelphia, and colleagues. Datopotamab deruxtecan is an antibody-drug conjugate consisting of a humanized anti-TROP2 immunoglobulin G1 monoclonal antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. Dr. Borghaei discussed the trial design during the International Association for the Study of Lung Cancer (IASLC) 2021 World Conference on Lung Cancer (Abstract P47.06).
In TROPION-Lung04, with about 20 international participating sites, datopotamab deruxtecan will be given to patients with advanced or metastatic NSCLC who do not have actionable genomic alterations. All medications will be given three times weekly in part 1 (dose escalation) to a patient population divided into six cohorts: Those in cohorts 1, 3, and 5 will receive 4 mg/kg of datopotamab deruxtecan; those in cohorts 2, 4, and 6 will receive 6 mg/kg. All patients will receive datopotamab deruxtecan in combination with 1,120 mg of the monoclonal antibody durvalumab; those in cohorts 3 and 4 will also receive four cycles of carboplatin AUC 5, and those in cohorts 5 and 6 will also receive cisplatin at 75 mg/m2.
The study’s primary objective, said Dr. Borghaei, is to assess the safety and tolerability of datopotamab deruxtecan. This includes but is not limited to dose-limiting toxicities (part 1) and treatment-emergent adverse events and adverse events of special interest (parts 1 and 2). The secondary objectives for both parts of the study, he added, include overall response rate, duration of response, progression-free survival, overall survival, pharmacokinetics, and incidence of antidrug antibodies.
Disclosure: The study authors reported no conflicts of interest.