Dose-escalation results from a phase 1-2 trial of ifinatamab deruxtecan, a B7-H3-directed antibody-drug conjugate, for advanced solid tumors

Ifanatamb deruxtecan (I-DXd) ia novel B7-H3-directed antibody-drug conjugate. Dose-escalation results from the phase 1-2 IDeate-PanTumor01 trial at ten centers in Japan and the USA have been published. The trial enrolled 97 adult patients with advanced treatment-refractory solid tumors, who received I-DXd at doses of 0.8-16.0 mg/kg intravenously every 3 weeks. The primary outcome was safety. Three patients (3%) had dose-limiting toxities, however, on the basis of protocol-defined criteria, the maximum tolerated dose was not reached. Serious treatment-emergent adverse events occurred in 31 patients (32%). TEAEs associated with death were reported in five patients (5%). One death due to interstitial lung disease (ILD) was considered related to study medication by the investigator.After a median follow-up of 8.6 months (IQR 4.1-12.9), the confirmed objective response rate across tumor types was 34% (95% CI 23-47).The authors conclude that the maximum tolerated dose was not reached with I-DXd; however, one death due to treatment-related ILD highlights the importance of prompt evaluation and careful management of patients who develop ILD. Promising antitumor activity was observed across various solid tumors.