Daiichi Sankyo and Merck withdraw the U.S. BLA for ifinatamab deruxtecan in previously treated ES-SCLC after FDA discussions on accelerated approval.
Written By: Anshu Gupta, PharmD
Reviewed By: Pharmacally Editorial Team
Daiichi Sankyo and Merck have voluntarily withdrawn the U.S. Biologics License Application (BLA) seeking accelerated approval for investigational ifinatamab deruxtecan (I-DXd) in adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has progressed on or after platinum-based chemotherapy.
The decision follows discussions with the U.S. Food and Drug Administration (FDA), during which the companies said the available data supporting the application, including findings from the Phase 2 IDeate-Lung01 trial, did not satisfy the requirements needed to support accelerated approval for the proposed indication.
FDA Priority Review Preceded BLA Withdrawal
The BLA had previously received FDA Priority Review, with an original Prescription Drug User Fee Act (PDUFA) target action date of October 10, 2026.
The withdrawal applies to the current accelerated-approval application and does not represent discontinuation of the broader clinical development of ifinatamab deruxtecan.
Phase 2 IDeate-Lung01 Study
IDeate-Lung01 (NCT05280470) was a global, multicenter, randomized, open-label, two-part Phase 2 study evaluating ifinatamab deruxtecan in patients with ES-SCLC previously treated with platinum-based chemotherapy.
The study enrolled 187 patients across Asia, Europe and North America. In the dose-optimization portion, patients were randomized to receive ifinatamab deruxtecan at 8 mg/kg or 12 mg/kg intravenously once every three weeks. In the dose-expansion portion, patients received 12 mg/kg on the same schedule.
In the 12 mg/kg population, ifinatamab deruxtecan demonstrated a confirmed objective response rate (ORR) of 48.2% and a median progression-free survival (PFS) of 4.9 months.
The primary endpoint was ORR assessed by blinded independent central review according to RECIST version 1.1. Secondary endpoints included duration of response, PFS, disease control rate, time to response, overall survival, pharmacokinetics and safety. Intracranial ORR was assessed as an exploratory endpoint.
Despite these findings, the companies said discussions with the FDA indicated that the available dataset did not meet the requirements needed to support accelerated approval.
Phase 3 IDeate-Lung02 Remains Ongoing
Patient enrollment continues in the Phase 3 IDeate-Lung02 trial (NCT06203210), which is evaluating ifinatamab deruxtecan versus physician’s choice of chemotherapy in patients with relapsed ES-SCLC following disease progression after only one prior line of platinum-based chemotherapy.
Physician’s-choice chemotherapy options include amrubicin, lurbinectedin and topotecan. Enrollment in IDeate-Lung02 is nearing completion.
Unlike the Phase 2 study, IDeate-Lung02 is a randomized Phase 3 trial with dual primary endpoints of BICR-assessed ORR and overall survival (OS). The study is designed to generate comparative efficacy and safety data for ifinatamab deruxtecan against physician’s choice chemotherapy.
The companies said results from IDeate-Lung02 could be evaluated as the basis for a potential future filing with the FDA and other global regulatory authorities.
Development Continues in Other Cancers
Ifinatamab deruxtecan is also being evaluated in additional Phase 3 studies in advanced or metastatic cancers.
The IDeate-Prostate01 trial (NCT06925737) is evaluating the therapy in patients with castration-resistant prostate cancer (CRPC), while IDeate-Esophageal01 (NCT06644781) is evaluating ifinatamab deruxtecan in esophageal squamous cell carcinoma (ESCC).
These studies remain part of the broader clinical development program.
Investigational B7-H3-Directed ADC
Ifinatamab deruxtecan is an investigational B7-H3-directed antibody-drug conjugate (ADC) developed using Daiichi Sankyo’s proprietary DXd ADC technology. The therapy consists of a humanized anti-B7-H3 IgG1 monoclonal antibody linked to topoisomerase I inhibitor payloads derived from exatecan through tetrapeptide-based cleavable linkers.
B7-H3 is a transmembrane protein belonging to the B7 family and is expressed across multiple cancer types, including SCLC. According to the companies, no B7-H3-directed medicine is currently approved for cancer treatment.
Ifinatamab deruxtecan has received orphan drug designation for SCLC from the U.S. FDA, European Commission, Japan Ministry of Health, Labour and Welfare, and Taiwan Food and Drug Administration. The FDA has also granted orphan drug designation for the therapy in esophageal cancer.
Regulatory Path Forward
With IDeate-Lung02 nearing completion and additional Phase 3 studies underway, future regulatory evaluation of ifinatamab deruxtecan in ES-SCLC will depend on data generated through these studies. The companies said they will assess the potential for future regulatory filings based on the Phase 3 results.
Reference
Ifinatamab Deruxtecan Biologics License Application for Certain Patients with Previously Treated Extensive-Stage Small Cell Lung Cancer Voluntarily Withdrawn, Merck, 25 September 2026
Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01), ClinicalTrials.gov ID NCT05280470
About the Writer
Anshu Gupta (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, regulatory affairs, and medical writing. She has presented research at academic conferences and completed certifications in Good Clinical Practice (GCP), ICH-GCP, and drug safety. Passionate about clinical trials and evidence-based medicine, she is committed to translating scientific evidence into accurate, reliable, and accessible healthcare content.