Lurbinectedin

iStock, Suchat longthara The fatalities were attributed to interstitial lung disease, a known side effect of Daiichi Sankyo’s DXd-based antibody-drug conjugates. A spokesperson declined to say how many patients died. 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-Lung02—the same study that is now under partial hold. 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 .

The Food and Drug Administration has put a partial clinical hold on one of Merck & Co. and Daiichi Sankyos antibody-drug conjugates following an unexpected number of deaths in a late-stage clinical trial.Daiichi initiated a voluntary pause recruiting and enrolling the trial, called IDeate-Lung02, after higher than anticipated incidence of grade 5 interstitial lung disease events, a spokesperson for Merck and Daiichi said in a statement to BioPharma Dive. Following the pause, the FDA verbally placed the trial on a partial clinical hold in October. The spokesperson did not say the number of deaths recorded.During the hold, Daiichi, along with the FDA and an independent committee will review the safety data and decide on any necessary further actions. Trial enrollees will be able to continue treatment, but no new participants will be recruited.The experimental drug, called ifinatamab deruxtecan, or I-DXd, is one of three ADCs Merck gained the rights to through a major licensing deal with Daiichi in 2023. ADCs, which link an antibody to a toxic payload, are meant to more effectively target and destroy cancer cells while sparing the surrounding healthy tissue.Though theyve been around for decades, ADCs became a major asset for drug developers relatively recently. AstraZeneca and Daiichi, for instance, found success with their medicines Enhertu and Datroway, which are approved to treat several cancers. However, interstitial lung disease is a known side effect of Daiichis antibody-drug conjugates, and is listed on the labeling of Datroway and Enhertu.The Phase 3 trial testing I-DXd enrolled over 500 participants with small cell lung cancer, who were treated with the drug or randomized to receive a chemotherapy regimen of either topotecan, lurbinectedin or amrubicin.Expectations for the drug rose after Phase 2 results demonstrated promising objective response rates in people with pretreated, extensive-stage small cell lung cancer. The FDA granted breakthrough therapy designation to I-DXd based on those results.The spokesperson said the companies are in discussions with global regulatory authorities over the latest trial data, but would not comment further on regulatory strategy.The clinical hold represents another blow to Mercks ADC program. Earlier this year, the company pulled its approval application for a therapy called patritumab deruxtecan, after finding it did not extend survival in people who have a certain kind of non-small cell lung cancer with mutations in the EGFR gene. The FDA also rejected patritumab deruxtecan last year due to third-party manufacturing problems.The spokesperson said the clinical hold does not impact other studies of I-DXd.Merck and Daiichi are evaluating the potential impact of the hold on trial readout data timing, which is currently expected in 2027. '