The FDA initially placed the Phase III IDeate-Lung02 study on hold due to a “higher than expected” number of deaths in patients treated with ifinatamab deruxtecan.
The FDA has lifted its partial clinical hold on Merck and Daiichi Sankyo’s ifinatamab deruxtecan, an antibody-drug conjugate being tested for lung cancer, a spokesperson for the companies confirmed to BioSpace in an email on Monday.
With the freeze lifted, Merck and Daiichi Sankyo can now proceed with their planned Phase III IDeate-Lung02 study of ifinatamab deruxtecan, also called I-DXd, in relapsed small cell lung cancer. The trial remains paused in the European Union, however. The partners are continuing to work with the European Medicines Agency toward lifting this hold, the spokesperson added.
IDeate-Lung02 was placed under partial clinical hold last month after the FDA detected a “higher than expected” rate of deaths in patients treated with I-DXd, related to interstitial lung disease (ILD).
The spokesperson said that Merck and Daiichi Sankyo have implemented “additional strategies” to mitigate the risk of pneumonitis and ILD. These strategies include “stricter trial enrollment eligibility criteria” and “more frequent review of unblinded efficacy and safety data.”
The companies have also implemented additional training for investigators and clinical study staff, the spokesperson added.
Original story published Dec. 19, 2025.
Patient Deaths Put Merck, Daiichi Sankyo’s Antibody-Drug Conjugate on Hold
The FDA has placed a partial clinical hold on Merck and Daiichi Sankyo’s late-stage development program for their antibody-drug conjugate ifinatamab deruxtecan after “a higher than expected” number of deaths were detected, according to several media reports on Thursday.
The companies were studying ifinatamab deruxtecan—more commonly known as I-DXd—in the Phase III IDeate-Lung02 trial, which has enrolled more than 500 patients with relapsed small cell lung cancer. Participants were treated with I-DXd or with an active chemotherapy comparator, including topotecan, amrubicin and lurbinectedin.
In a joint statement to Fierce Biotech, a spokesperson for the companies said that they detected “a higher than anticipated incidence of grade 5 interstitial lung disease (ILD) events” in IDeate-Lung02, which prompted Daiichi Sankyo to voluntarily halt recruitment. The FDA has since also applied a partial freeze on the study.
The spokesperson did not indicate how many patients died.
“ILD is a potentially fatal side effect known to be associated with all of Daiichi’s DX ADCs [antibody-drug conjugates],” Jefferies analysts explained in a Thursday note to investors. “This has not stopped Enhertu and Datroway from being approved.”
The spokesperson said that the hold “does not impact other studies in the I-DXd clinical development program.” The partners are working with the regulator and with an independent data board to best understand the mortalities and determine the next steps for the affected study.
Merck and Daiichi Sankyo teamed up in October 2023 to collaborate on three DXd-based ADCs—anti-cancer constructs that consist of an antibody and an exatecan derivative, which is a topoisomerase I inhibitor that causes cancer cells to die.
In June 2024, the partners ran into a regulatory roadblock when the FDA declined to approve patritumab deruxtecan for locally advanced or metastatic non-small cell lung cancer. The rejection hinged on third-party manufacturing problems; the FDA did not identify issues with the drug’s efficacy or safety. The companies rallied in September of this year when I-DXd showed a 48.2% confirmed objective response rate in IDeate-Lung01 Phase II.
Aside from Merck, AstraZeneca has also bought into the promise of Daiichi Sankyo’s DXd platform. The partners have secured two approvals: one in late 2019 for Enhertu and another in January this year for Datroway.
Correction (Jan. 2, 2026): This story has been updated to reflect that last September’s results came from the IDeate-Lung01 Phase II, not the IDeate-Lung02 Phase III trial that is now under partial hold.
