Behind the FDA Approval of Dato-DXd in Lung Cancer With Dr Sands

In an interview with Targeted Oncology, Jacob Sands, MD, medical oncologist at Dana-Farber Cancer Center, discusses the data that support the FDA accelerated approval of datopotamab deruxtecan (Dato-DXd; Datroway) in adult patients with locally advanced or metastatic EGFR-mutated non–small cell lung cancer (NSCLC) who have previously received systemic therapies, including EGFR-targeted treatments.

The approval is based on a pooled efficacy analysis from 2 clinical trials: TROPION-Lung05 (NCT04484142), a multicenter, single-arm phase 2 trial; and TROPION-Lung01 (NCT04656652), a global, open-label phase 3 study. Sands was an investigator on the TROPION-Lung studies and provides his insight into the data.

Among 114 patients meeting the labeled criteria, the confirmed overall response rate (ORR) was 45% (95% CI, 35%–54%), with a median duration of response of 6.5 months (95% CI, 4.2–8.4), as assessed by blinded independent central review using RECIST v1.1.

"What [TROPION-Lung01] demonstrated in patients who had previously gotten platinum-based therapy plus a checkpoint inhibitor, either concurrent or sequential in the nonactionable genomic [alteration cohort] or had gotten targeted therapy as well as platinum-based therapy in the in the population with actionable genomic alterations—what we saw from that was improvement in progression-free survival that was statistically significant with Dato-DXd as compared to docetaxel," Sands explains. "Butwhen we split to the squamous cohort, it actually trended better with docetaxel, and so the nonsquamous cohort had a more significant improvement in progression-free survival, as well as an overall survival that trended similar to what we saw from progression-free survival."

Dato-DXd is a TROP2-directed antibody-drug conjugate comprised of a humanized monoclonal antibody linked to a topoisomerase I inhibitor via a cleavable linker. It represents a novel, chemotherapy-free approach targeting TROP2-expressing NSCLC tumors following resistance to first-line therapies.

In previously reported findings from a larger pooled dataset (n = 117), the agent achieved an ORR of 42.7%, including 4.3% complete responses, with a disease control rate of 86.3% and a median progression-free survival (PFS) of 5.8 months. Median overall survival was 15.6 months, supporting the clinical benefit of Dato-DXd beyond traditional chemotherapeutics.