Optimal Datopotamab Deruxtecan Dose for Patients With Metastatic NSCLC

The first in-human study of datopotamab deruxtecan (Dato-DXd) showed the optimal dose for greater tumor response, PFS, and safety to be 6 mg/kg every 3 weeks compared with two other dosing regimens.

The phase 1 study evaluated three doses for patients with metastatic NSCLC: 4 mg/kg (n=50), 6 mg/kg (n=50), or 8 mg/kg (n=80). The maximum tolerated dose (MTD) was found to be 8 mg/kg.

Tumor size was measured at screening, every 6 weeks up to week 36, and then every 12 weeks while patients remained on Dato-DXd.

The 6-mg/kg dose was identified by Yasong Lu, MD, and colleagues as the optimal dose for patients because it was more tolerable than the MTD and more efficacious than Dato-DXd 4 mg/kg. Lower rates of interstitial lung disease were seen in the 6-mg/kg cohort than in the 8-mg/kg cohort (8% vs 15%, respectively). Moreover, patients in the 6-mg/kg cohort also experienced less stomatitis and mucosal inflammation compared with patients in the 8-mg/kg cohort.

Once the 8-mg/kg dose was stopped over safety concerns, analyses of the 6-mg/kg and 4-mg/kg doses showed that Dato-DXd 6 mg/kg provided a better mean objective response rate than Dato-DXd 4 mg/kg (23.8% vs 18.6%, respectively). The mean hazard ratio of PFS was 0.74.

Because Dato-DXd 6 mg/kg demonstrated an optimal benefit-risk profile, the researchers recommended this dose for late-phase development.