TROPION-Lung05: Datopotamab Deruxtecan Shows ‘Encouraging’ Activity in NSCLC

Datopotamab deruxtecan showed “encouraging and durable antitumor activity” in patients with heavily pretreated advanced or metastatic non-small cell lung cancer (NSCLC) who had actionable genomic alterations, according to results from TROPION-Lung05.

Jacob Sands, MD, of the Dana-Farber Cancer Institute in Boston, and colleagues conducted the study and published their findings in the Journal of Clinical Oncology.

The phase 2 trial evaluated the safety and clinical activity of the TROP2-directed antibody-drug conjugate in patients who had advanced or metastatic NSCLC with actionable genomic alterations and progression on or after targeted therapy and platinum-based chemotherapy.

The patients in the study received datopotamab deruxtecan 6 mg/kg once every three weeks. Among the 137 patients who received at least one dose of the antibody-drug conjugate, 71.5% had received at least three lines of prior therapy for advanced or metastatic disease. Most patients had EGFR mutations (56.9%) or ALK rearrangements (24.8%). The median duration of treatment was 4.4 months (range, 0.7-20.6).

The primary endpoint of the TROPION-Lung05 trial was objective response rate (ORR) by blinded independent central review, with secondary endpoints including duration of response (DOR), safety, tolerability, and survival.

The TROPION-Lung05 trial showed a confirmed ORR of 35.8% (95% CI, 27.8 to 44.4) in the overall population. The confirmed ORR was 43.6% (95% CI, 32.4 to 55.3) in patients with EGFR mutations and 23.5% (95% CI, 10.7 to 41.2) in those with ALK rearrangements. The median DOR was seven months (95% CI, 4.2 to 9.8), with an overall disease control rate of 78.8% (95% CI, 71.0 to 85.3).

Treatment-related adverse events (TRAEs) of grade 3 or higher occurred in 28.5% of patients, with stomatitis being the most common TRAE. Any grade stomatitis occurred in 56.2%, with grade 3 and higher occurring in 9.5%. Adjudicated treatment-related interstitial lung disease/pneumonitis occurred in five (3.6%) patients, with one (0.7%) grade 5 event.

“The rate of treatment-related grade ≥3 toxicities was comparable with previous observations, and no new safety signals were observed,” Dr. Sands and colleagues wrote.

Based on the results from TROPION-Lung05, Dr. Sands and colleagues concluded that the antibody-drug conjugate showed “encouraging and durable antitumor activity” in this population of patients.

Source: Journal of Clinical Oncology