FDA places partial clinical hold on Merck and Daiichi Sankyo’s I-DXd lung cancer trial after interstitial lung disease deaths
The FDA has imposed a partial clinical hold on Merck and Daiichi Sankyo’s Phase 3 IDeate-Lung02 trial of the antibody-drug conjugate ifinatamab deruxtecan (I-DXd) in small cell lung cancer.13
The action follows a “higher than anticipated incidence of grade 5 interstitial lung disease (ILD) events” (grade 5 = fatal), which led to several patient deaths in the study.123
Before the FDA step, Daiichi Sankyo had already voluntarily paused recruitment and enrollment in IDeate-Lung02 after detecting the excess fatal ILD events.13
Under the partial hold, no new patients will be enrolled, but current participants may continue treatment while safety is reviewed by the FDA, Daiichi Sankyo, Merck, and an independent monitoring committee.13
The exact number of deaths has not been disclosed, but company representatives and registry entries confirm that they were attributed to ILD, a known risk of Daiichi Sankyo’s DXd-based ADCs.123
IDeate-Lung02 enrolled over 500 patients with relapsed or refractory extensive-stage small cell lung cancer, comparing I-DXd against chemotherapy options such as topotecan, lurbinectedin, or amrubicin.13
I-DXd is one of three DXd-based ADCs that Merck licensed from Daiichi Sankyo in 2023 in a multi‑billion‑dollar oncology deal, making this safety issue a notable setback for the collaboration.123
The partial hold specifically affects the late-stage IDeate-Lung02 program; earlier data from the Phase 2 IDeate-Lung01 trial had shown promising activity but also documented treatment-related deaths, underscoring ILD as a key safety risk to manage.15
Regulators and the companies are now conducting a comprehensive safety review to determine if protocol changes, additional monitoring, dose modifications, or other risk‑mitigation steps are needed before any potential restart of enrollment.13
Sources:
1. https://www.biopharmadive.com/news/merck-daiichi-sankyo-clinical-hold-ifinatamab-deruxtecan/808385/
2. https://www.oncologypipeline.com/apexonco/lung-toxicity-deaths-halt-ifinatamab