Ifinatamab deruxtecan

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. '

Daiichi will work with the FDA and an independent data monitoring committee to review safety data and “determine any necessary further actions,” a spokesperson told Fierce.\n Daiichi Sankyo and Merck & Co.’s phase 3 program for their investigational antibody-drug conjugate has been hit with a hold after an unexpected number of deaths were reported in the global trial.“Due to a higher than anticipated incidence of grade 5 interstitial lung disease (ILD) events identified in the IDeate-Lung02 phase 3 trial, Daiichi Sankyo initiated a voluntary pause in recruitment and enrollment,” a spokesperson for the partners told Fierce Biotech. The companies did not answer questions regarding how many deaths have occurred.“Following the initial pause, the FDA has placed the trial on a partial clinical hold,” the spokesperson explained.The unexpected deaths come as the pharma partners said they were aiming for an accelerated approval of the investigational B7-H3-directed ADC—known as ifinatamab deruxtecan or I-DXd—for pretreated small cell lung cancer (SCLC) based on a phase 2 readout. In 2023, Merck paid out $5.5 billion in upfront and near-term payments to gain access to a clutch of Daiichi’s ADCs.Under the hold, Daiichi will work with the FDA and an independent data monitoring committee to review safety data and “determine any necessary further actions,” the spokesperson told Fierce.“Of note, it does not impact other studies in the I-DXd clinical development program,” the spokesperson added.Patients currently enrolled in IDeate-Lung02 will be able to continue treatment, but no new participants will be recruited during this time, according to the spokesperson.“We are evaluating the potential impact of the partial clinical hold on study data readout timing, currently projected for fiscal year 2027,” the spokesperson said.The deaths and consequential hold have not been announced publicly by either Merck or Daiichi, but instead were first reported by oncology-focused publication ApexOnco. The temporary halts began in several European countries—such as France, Germany and Italy—at the end of September, according to the European clinical trial registry. In September, Merck and Daiichi shared phase 2 IDeate-Lung01 data demonstrating an objective response rate (ORR) of 48.2% among 137 patients receiving 12 mg/kg of I-DXd—findings the companies thought would help score accelerated approval in SCLC. While an accelerated approval tag has not yet materialized, the ADC does tout an FDA breakthrough therapy status that it secured in August.“The important take-home message is that this is our registrational trial for the first approval of the drug I-DXd,” Daiichi’s R&D head Ken Takeshita, M.D., told Fierce Biotech about the phase 2 findings in September.Takeshita underscored I-DXd’s durability in a population that doesn’t have many treatment options, with the data showing a median duration of response of 5.3 months and a disease control rate of 87.6%.Overall, 89.8% of patients experienced a treatment-related adverse event (TRAE) in the mid-stage program, with 36.5% experiencing a grade 3 or higher event. Thirteen patients (9.5%) had a TRAE associated with treatment discontinuation, while six (4.4%) patient deaths were deemed to be related to treatment.Considering the advanced nature of the cancer I-DXd is aiming to treat, Takeshita said at the time that Daiichi believed the risk-benefit analysis favored the investigational drug. “As previously announced, discussions with global regulatory authorities are underway regarding the latest data available from IDeate-Lung01,” the spokesperson told Fierce today. “We cannot comment further on our regulatory strategy.”Beyond Ideate-Lung02, the pharma partners are running two other pivotal programs for I-DXd, one in metastatic castration-resistant prostate cancer and another in advanced esophageal squamous cell carcinoma.This isn’t the first hit to Merck’s major ADC deal with Daiichi. This spring, the partners pulled their biologics license application for ADC patritumab deruxtecan—also known as HER3-DXd—for patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC) who\'ve been previously treated with two or more systemic therapies.Topline overall survival results from a phase 3 study that didn’t meet statistical significance, plus discussions with the FDA, factored into the withdrawal. In that trial, ILD—the lung condition that the new deaths have been attributed to—occurred in 14 patients (5%) treated with HER3-DXd, with two of the cases resulting in death.  The FDA had also already rejected HER3-DXd last year based on \"findings pertaining to an inspection of a third-party manufacturing facility,\" Daiichi said previously.