Dr. Kato on the Rationale For Investigating Dato-DXd Plus Durvalumab and Carboplatin in Advanced NSCLC

Terufumi Kato, MD, Chief Physician, Department of Thoracic Oncology, Kanagawa Cancer Center, Yokohama, Japan, discusses the ongoing investigation of datopotamab deruxtecan (Dato-DXd; DS-1062a) in combination with durvalumab (Imfinzi) and carboplatin in the as a first-line treatment for patients with advanced metastatic non–small cell lung cancer (NSCLC).

Dato-DXd is an antibody-drug conjugate (ADC) consisting of a humanized anti-TROP2 IgG1 monoclonal antibody linked to a potent topoisomerase-I inhibitor via a tumor-selective cleavable linker, Kato begins. Early clinical investigations have shown encouraging efficacy and safety with this agent in advanced metastatic disease, but the ability to predict efficacy based on TROP2 expression remains to be determined, Kato notes.

The ongoing, multicenter, open-label, randomized phase 3 AVANZAR study (NCT05687266) aims to evaluate whether the combination of Dato-DXd anddurvalumab with carboplatin can improve outcomes for patients with stage IIIB, IIIC, or IV metastatic NSCLC vs pembrolizumab (Keytruda) and chemotherapy, Kato details. Eligible patients must have squamous or non-squamous histology and must not display sensitizing EGFR mutations or ALK and ROS1 rearrangements, he adds. Additionally, all patients must have locally advanced or metastatic NSCLC without prior exposure to first-line therapy targeting specific gene alterations.

Patients will be stratified by PD-L1 status, histology, smoking status, and TROP2 biomarker status, Kato states. Patients will then be randomly assigned 1:1 to receive either the experimental combination or a histology-specific chemotherapy plus pembrolizumab, Kato details. Treatment will continue until disease progression, unmanageable toxicity, or patient withdrawal from the study.

The study's primary endpoints are PFS by blinded independent review and OS in the TROP2-positive population, Kato states. Enrollment onto the study is ongoing, and the estimated date of study completion is May, 2027. Investigators plan to recruit 1,000 patients from approximately 230 study locations in an estimated 24 countries.