The FDA has imposed a partial clinical hold on the late-stage development of ifinatamab deruxtecan, an antibody-drug conjugate (ADC) developed by Merck and Daiichi Sankyo. This decision follows reports of an unexpectedly high number of patient deaths in the Phase III IDeate-Lung02 trial, which involves more than 500 patients with relapsed small cell lung cancer.
Patients in the study received either I-DXd or a chemotherapy comparator such as topotecan, amrubicin, or lurbinectedin. In a joint statement to Fierce Biotech, a spokesperson for Merck and Daiichi Sankyo said, “a higher than anticipated incidence of grade 5 interstitial lung disease (ILD) events” was observed in the trial. As a result, Daiichi Sankyo voluntarily stopped recruitment for the study before the FDA implemented its partial hold. The companies did not disclose how many patients died.
According to Jefferies analysts, “ILD is a potentially fatal side effect known to be associated with all of Daiichi’s DX ADCs [antibody-drug conjugates]. This has not stopped Enhertu and Datroway from being approved.” The spokesperson added that this clinical hold “does not impact other studies in the I-DXd clinical development program.” Both companies are working with regulators and an independent data board to review the fatalities and determine next steps for the affected trial.
Merck and Daiichi Sankyo began their collaboration in October 2023 to develop three DXd-based ADCs. These anti-cancer agents combine an antibody with an exatecan derivative—a topoisomerase I inhibitor designed to kill cancer cells.
Earlier regulatory challenges have affected this partnership. In June 2024, the FDA declined approval for patritumab deruxtecan due to third-party manufacturing issues rather than concerns about efficacy or safety. However, by September 2024, I-DXd had shown promising results in IDeate-Lung02 with a confirmed objective response rate of 48.2%, prior to the current clinical hold.
Daiichi Sankyo’s DXd platform has also attracted interest from AstraZeneca. Together they have achieved two regulatory approvals: one for Enhertu in late 2019 and another for Datroway in January 2025.
