Ifinatamab deruxtecan BLA withdrawal has been announced by Merck and Daiichi Sankyo after the companies voluntarily withdrew their U.S. Biologics License Application seeking accelerated approval for the investigational treatment in certain patients with previously treated extensive-stage small cell lung cancer (ES-SCLC).
The application was seeking accelerated approval for adult patients with ES-SCLC whose disease had progressed on or after platinum-based chemotherapy. According to Merck, the decision followed discussions with the U.S. Food and Drug Administration (FDA), during which the companies determined that the data supporting the application, including data from the Phase 2 IDeate-Lung01 trial, did not satisfy the requirements needed to support accelerated approval for the proposed indication.
The withdrawal concerns the current U.S. regulatory application and does not represent an end to the clinical development program for ifinatamab deruxtecan. Merck said patient enrollment is continuing in the Phase 3 IDeate-Lung02 study, which is evaluating the efficacy and safety of ifinatamab deruxtecan against physician’s choice of chemotherapy in patients with relapsed ES-SCLC following progression after one prior line of platinum-based chemotherapy.
Ifinatamab Deruxtecan BLA Withdrawal Follows FDA Discussions
The central development in the regulatory update is the voluntary withdrawal of the BLA. Merck and Daiichi Sankyo stated that discussions with the FDA indicated that the available data did not meet the requirements for accelerated approval of ifinatamab deruxtecan for the proposed ES-SCLC indication.
The companies specifically identified data from the Phase 2 IDeate-Lung01 study as part of the evidence supporting the application. The regulatory decision therefore relates to whether the submitted clinical evidence was sufficient to support accelerated approval for the proposed patient population at this stage of development.
The companies are continuing to evaluate ifinatamab deruxtecan in ES-SCLC through the ongoing Phase 3 development program. Merck and Daiichi Sankyo indicated that enrollment in IDeate-Lung02 is near completion and that results from the study could support a future regulatory filing.
IDeate-Lung01 Phase 2 Trial Evaluated Ifinatamab Deruxtecan
The IDeate-Lung01 study was a Phase 2 global, multicenter, randomized, open-label, two-part clinical trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with ES-SCLC who had previously received at least one line of platinum-based chemotherapy and a maximum of three prior lines of therapy.
The study enrolled 187 patients across Asia, Europe and North America. Patients with asymptomatic brain metastases, including untreated or previously treated brain metastases, were eligible to participate. Patients with certain forms of interstitial lung disease or pneumonitis requiring steroid treatment, current ILD/pneumonitis at screening, or clinically severe pulmonary compromise caused by intercurrent pulmonary illnesses were not eligible.
The first part of IDeate-Lung01 was designed for dose optimization. Patients were randomized in a 1:1 ratio to receive ifinatamab deruxtecan at either 8 mg/kg or 12 mg/kg, administered intravenously once every three weeks.
In the second part, which was the dose-expansion portion of the study, patients received ifinatamab deruxtecan at 12 mg/kg intravenously once every three weeks.
IDeate-Lung01 Key Study Details
| Parameter | Details |
|---|---|
| Study | IDeate-Lung01 |
| Clinical phase | Phase 2 |
| Trial number | NCT05280470 |
| Disease | Extensive-stage small cell lung cancer |
| Prior treatment | At least one prior line of platinum-based chemotherapy |
| Maximum prior lines | Three prior lines of therapy |
| Geographic scope | Asia, Europe and North America |
| Number enrolled | 187 patients |
| Trial design | Global, multicenter, randomized, open-label, two-part |
| Dose-optimization doses | 8 mg/kg and 12 mg/kg |
| Dose-expansion dose | 12 mg/kg |
| Administration | Intravenous |
| Dosing interval | Once every three weeks |
| Primary endpoint | Objective response rate |
| Response assessment | Blinded independent central review using RECIST v1.1 |
| Secondary endpoints | Duration of response, progression-free survival, disease control rate, time to response, overall survival, pharmacokinetics and safety |
| Exploratory assessment | Intracranial objective response rate |
IDeate-Lung02 Continues Phase 3 Evaluation
Despite the BLA withdrawal, the clinical development program for ifinatamab deruxtecan in ES-SCLC is continuing.
The Phase 3 IDeate-Lung02 trial is evaluating ifinatamab deruxtecan against physician’s choice of chemotherapy. The chemotherapy options specified by Merck are amrubicin, lurbinectedin or topotecan.
The study is evaluating patients with relapsed ES-SCLC following disease progression after only one prior line of platinum-based chemotherapy. Merck said enrollment in IDeate-Lung02 is near completion.
The companies indicated that results from this Phase 3 study will be important to assessing the potential for a future filing with the FDA and other global regulatory authorities.
Ifinatamab Deruxtecan Clinical Development in ES-SCLC
| Development element | Details |
|---|---|
| Investigational medicine | Ifinatamab deruxtecan |
| Disease | Extensive-stage small cell lung cancer |
| Current U.S. BLA status | Voluntarily withdrawn |
| Regulatory pathway sought | Accelerated approval |
| Earlier supporting study | IDeate-Lung01 |
| IDeate-Lung01 phase | Phase 2 |
| Confirmatory/current Phase 3 study | IDeate-Lung02 |
| Phase 3 comparator | Physician’s choice of chemotherapy |
| Comparator treatments | Amrubicin, lurbinectedin or topotecan |
| Patient setting | Relapsed ES-SCLC |
| Prior platinum therapy | One prior line |
| Current development status | Patient enrollment continuing; enrollment described as near completion |
What Is Ifinatamab Deruxtecan?
Ifinatamab deruxtecan is an investigational antibody-drug conjugate (ADC) designed to target B7-H3.
According to Merck, the medicine is designed using Daiichi Sankyo’s proprietary DXd ADC Technology. It consists of a humanized anti-B7-H3 IgG1 monoclonal antibody connected to topoisomerase I inhibitor payloads, specifically an exatecan derivative known as DXd, through tetrapeptide-based cleavable linkers.
The investigational ADC is being studied across multiple cancer types. Merck describes it as a potential first-in-class B7-H3-directed ADC.
At the time of the September 25, 2026 announcement, Merck stated that there were no B7-H3-directed medicines approved for the treatment of cancer.
Ifinatamab Deruxtecan: Drug and Mechanism Data
| Attribute | Details |
|---|---|
| Drug | Ifinatamab deruxtecan |
| Development code | I-DXd |
| Merck code | MK-2400 |
| Drug class | Antibody-drug conjugate |
| Target | B7-H3 |
| Antibody component | Humanized anti-B7-H3 IgG1 monoclonal antibody |
| Payload | Topoisomerase I inhibitor |
| Payload technology | DXd / exatecan derivative |
| Linker | Tetrapeptide-based cleavable linker |
| Development partners | Daiichi Sankyo and Merck |
| Regulatory status in cited announcement | Investigational |
B7-H3 Is the Target Behind Ifinatamab Deruxtecan
B7-H3 is a transmembrane protein belonging to the B7 family of proteins. Merck describes B7-H3 as being highly expressed across a broad range of cancer types, including small cell lung cancer.
The company states that B7-H3 overexpression has been shown to correlate with poor prognosis and describes the protein as a promising therapeutic target. Merck also states that there were no B7-H3-directed cancer medicines approved at the time of its announcement.
For ifinatamab deruxtecan, the B7-H3-directed antibody component is linked to the DXd topoisomerase I inhibitor payload. The investigational ADC is intended to use this targeted approach as part of its development across difficult-to-treat cancers.
Ifinatamab Deruxtecan Development Extends Beyond SCLC
The withdrawal of the U.S. BLA does not apply to the entire ifinatamab deruxtecan development program.
Merck said two additional Phase 3 trials are underway in advanced or metastatic disease: IDeate-Prostate01 in castration-resistant prostate cancer (CRPC) and IDeate-Esophageal01 in esophageal squamous cell carcinoma (ESCC).
The company described the overall development program as evaluating ifinatamab deruxtecan both as monotherapy and in combination with other cancer medicines across multiple cancer types.
Ifinatamab Deruxtecan Phase 3 Program
| Phase 3 program | Cancer type |
|---|---|
| IDeate-Lung02 | Extensive-stage small cell lung cancer |
| IDeate-Prostate01 | Castration-resistant prostate cancer |
| IDeate-Esophageal01 | Esophageal squamous cell carcinoma |
Merck and Daiichi Sankyo Continue Collaboration
Ifinatamab deruxtecan is being developed through a global collaboration between Daiichi Sankyo and Merck.
The companies entered into their global collaboration in October 2023 to jointly develop and commercialize ifinatamab deruxtecan, raludotatug deruxtecan and patritumab deruxtecan, with Daiichi Sankyo retaining exclusive rights in Japan for those programs.
Under the collaboration described by Merck, Daiichi Sankyo is responsible for manufacturing and supply of these medicines. The collaboration was expanded in August 2024 to include gocatamig, which the companies agreed to jointly develop and commercialize worldwide except in Japan, where Merck retains exclusive rights.
What the Ifinatamab Deruxtecan BLA Withdrawal Means for Development
The immediate regulatory consequence is that the U.S. BLA seeking accelerated approval for ifinatamab deruxtecan in the specified previously treated ES-SCLC population has been voluntarily withdrawn.
The withdrawal follows the companies’ discussions with the FDA concerning whether the available evidence met the requirements for accelerated approval. Merck specifically cited the supporting data, including evidence from IDeate-Lung01, as not satisfying those requirements for the proposed indication.
The investigational medicine nevertheless remains in clinical development. The ongoing IDeate-Lung02 Phase 3 study represents a separate stage of evidence generation and is evaluating ifinatamab deruxtecan against established chemotherapy choices in relapsed ES-SCLC.
Accordingly, the September 25, 2026 announcement concerns the status of the specific U.S. BLA and should not be interpreted as a discontinuation of the overall ifinatamab deruxtecan clinical development program.
