NEW YORK – AstraZeneca and Daiichi Sankyo on Wednesday said they have begun three new Phase III trials to test the activity of the Trop2-targeted antibody-drug conjugate datopotamab deruxtecan (Dato-DXd) with other therapies in patients with high PD-L1 expressing or EGFR-mutated advanced or metastatic non-small cell lung cancer.
In TROPION-Lung10, the companies are comparing Dato-DXd plus AstraZeneca's PD-1/TIGIT-targeted bispecific antibody rilvegostomig versus rilvegostomig alone versus Merck's checkpoint inhibitor Keytruda (pembrolizumab) in about 675 patients with previously untreated, locally advanced, or metastatic non-squamous NSCLC. Patients must have PD-L1 expression in at least 50 percent of tumor cells, but they can't have other clinically actionable biomarkers such as EGFR mutations or ALK and ROS1 rearrangements. The researchers will track progression-free survival and overall survival in patients who test positive for Trop2 expression as the primary outcome measures of the trial. They will also monitor progression-free survival and overall survival in the intent-to-treat population and track other measures of efficacy, safety, and immunogenicity in all patients.
In the TROPION-Lung14 trial, researchers will compare Dato-DXd plus AstraZeneca's EGFR inhibitor Tagrisso (osimertinib) versus Tagrisso alone in about 600 patients with previously untreated, locally advanced, or metastatic EGFR-mutated non-squamous NSCLC. The trial's primary endpoint will be progression-free survival. The investigators are also assessing secondary outcome measures, including overall survival, central nervous system progression-free survival, overall response rate, and duration of response.
In TROPION-Lung15, AstraZeneca is comparing Dato-DXd with Tagrisso versus Dato-DXd monotherapy versus platinum-based doublet chemotherapy in about 630 patients with EGFR-mutated locally advanced or metastatic NSCLC. The primary objective of the trial is to assess how long patients receiving Dato-DXd with or without Tagrisso live without their disease progressing. Secondary endpoints will include overall survival, central nervous system progression-free survival, objective response rate, and duration of response.
"These three trials in either high PD-L1 expressing or EGFR-mutated non-squamous non-small cell lung cancer are critical to helping us understand the potential role of datopotamab deruxtecan in treating patients across different lines and types of lung cancer," Mark Rutstein, global head of oncology clinical development at Daiichi Sankyo, said in a statement.