U.S. Grants Priority Review to Ifinatamab Deruxtecan for Previously Treated ES-SCLC Patients After Platinum Therapy
Daiichi Sankyo and Merck & Co. have reached an important regulatory milestone with the U.S. Food and Drug Administration accepting their Biologics License Application (BLA) for ifinatamab deruxtecan (I-DXd). The application has been granted Priority Review for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) who have experienced disease progression during or after platinum-based chemotherapy. This designation underscores both the urgency of addressing unmet medical needs in this aggressive cancer type and the potential promise of this investigational therapy.
Under the Prescription Drug User Fee Act (PDUFA), the FDA has set a target action date of October 10, 2026, by which it is expected to complete its review and make a decision regarding approval. Priority Review status shortens the standard review timeline, reflecting the agency’s view that the therapy may offer meaningful clinical advantages compared to currently available treatment options.
Ifinatamab deruxtecan represents a next-generation approach in oncology therapeutics. It is an antibody-drug conjugate (ADC) designed to target B7-H3, a protein that is highly expressed in various solid tumors, including small cell lung cancer. As a DXd ADC, the therapy combines a tumor-targeting monoclonal antibody with a potent cytotoxic payload via a specialized linker, allowing for selective delivery of chemotherapy directly to cancer cells. This targeted mechanism is intended to maximize anti-tumor activity while minimizing systemic toxicity, a major limitation of conventional chemotherapy approaches.
The investigational agent was discovered by Daiichi Sankyo and is being co-developed in partnership with Merck, reflecting a growing trend of strategic collaborations aimed at accelerating innovation in oncology. Both companies have emphasized the importance of advancing therapies that can address difficult-to-treat cancers, particularly those like ES-SCLC, which are associated with poor prognosis and limited treatment options after initial therapy failure.
The FDA’s decision to grant Priority Review is based on data derived primarily from the Phase 2 IDeate-Lung01 clinical trial, with additional supportive evidence from the Phase 1/2 IDeate-PanTumor01 study. These trials evaluated the safety and efficacy of ifinatamab deruxtecan in patients with advanced cancers, including those with small cell lung cancer who had already undergone standard treatments. Results from the primary analysis of the IDeate-Lung01 study were presented at the World Conference on Lung Cancer 2025, organized by the International Association for the Study of Lung Cancer, and were subsequently published in the Journal of Clinical Oncology. The findings demonstrated encouraging anti-tumor activity and a manageable safety profile, supporting further regulatory evaluation.
In addition to Priority Review, the FDA is evaluating the BLA through two of its expedited programs: the Real-Time Oncology Review (RTOR) and Project Orbis. RTOR allows the FDA to review portions of a submission as they become available, rather than waiting for a complete application, thereby potentially accelerating the review timeline. Project Orbis, on the other hand, enables concurrent review of oncology therapies by multiple international regulatory agencies, promoting global collaboration and faster access to innovative treatments across different countries.
Ifinatamab deruxtecan has also previously received Breakthrough Therapy Designation from the FDA in August 2025 for the same patient population. This designation is reserved for therapies that show substantial improvement over existing treatments based on preliminary clinical evidence. Together with Priority Review, these regulatory pathways highlight the potential clinical significance of the therapy and the FDA’s commitment to facilitating its development.
Small cell lung cancer, particularly in its extensive-stage form, remains one of the most aggressive and challenging malignancies to treat. While initial responses to platinum-based chemotherapy can be significant, the majority of patients experience relapse, and treatment options in the second-line setting are limited and often associated with modest efficacy. The development of novel targeted therapies such as antibody-drug conjugates offers a promising avenue for improving outcomes in this patient population.
John Tsai, MD, Global Head of Research and Development at Daiichi Sankyo, described the Priority Review designation as a significant milestone in the company’s efforts to deliver innovative cancer treatments. He emphasized the importance of continued collaboration with the FDA to bring this potential first-in-class therapy to patients as quickly as possible.
Similarly, Eliav Barr, MD, Senior Vice President and Head of Global Clinical Development at Merck Research Laboratories, highlighted the urgent need for new treatment options in small cell lung cancer. He noted that the FDA’s acceptance of the BLA reinforces the potential role of ifinatamab deruxtecan in addressing the unmet needs of patients whose disease progresses after standard therapies.
The regulatory progress of ifinatamab deruxtecan reflects broader advancements in the field of oncology, where precision medicine and targeted therapies are increasingly transforming the treatment landscape. As the FDA continues its review, the oncology community will be closely watching for the final decision, which could introduce a novel therapeutic option for patients facing limited alternatives.
If approved, ifinatamab deruxtecan could represent a meaningful advancement in the treatment of extensive-stage small cell lung cancer, offering hope to patients and clinicians alike. The upcoming PDUFA date in October 2026 will be a critical moment in determining whether this promising therapy will become part of the standard treatment arsenal for this aggressive disease.
About IDeate-Lung01
IDeate-Lung01 is a global, multicenter, randomized, open-label, two-part Phase 2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with ES-SCLC who were previously treated with at least one prior line of platinum-based chemotherapy and a maximum of three prior lines of therapy. Patients with asymptomatic brain metastases (untreated or previously treated) were eligible to participate.
In the first part of the trial (dose optimization), patients were randomized 1:1 to receive ifinatamab deruxtecan (8 or 12 mg/kg) given intravenously once every three weeks. In the second part of the trial (dose expansion), patients received ifinatamab deruxtecan (12 mg/kg) intravenously at the same dosing interval.
The primary endpoint is objective response rate (ORR) as assessed by blinded independent central review (BICR) per RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), disease control rate (DCR), time to response (TTR), overall survival (OS), pharmacokinetics and safety. Intracranial ORR was assessed by BICR as an exploratory analysis.
IDeate-Lung01 enrolled 187 patients in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.
About IDeate-PanTumor01
IDeate-PanTumor01 is a global, multicenter, first-in-human, open-label Phase 1/2 trial evaluating the safety and efficacy of ifinatamab deruxtecan in patients with advanced/unresectable or metastatic solid tumors that are refractory or intolerable to standard treatment or for whom no standard treatment exists.
The Phase 1 part of the trial (dose escalation) is assessing the safety and tolerability of increasing doses of ifinatamab deruxtecan to determine the maximum tolerated dose and recommended dose for expansion (RDE). The Phase 2 part of the trial (dose expansion) is evaluating the safety and efficacy of ifinatamab deruxtecan at the RDE of 12 mg/kg in patients with squamous non-small cell lung cancer, metastatic castration-resistant prostate cancer or esophageal squamous cell carcinoma.
The dose escalation part of the trial is evaluating dose-limiting toxicity and safety. The dose expansion part of the trial is evaluating ORR, DOR, DCR, PFS, OS and safety. Pharmacokinetic endpoints, exploratory biomarker and immunogenicity endpoints also will be assessed.
IDeate-PanTumor01 will enroll approximately 250 patients in Asia and North America. For more information about the trial, visit ClinicalTrials.gov.
About small cell lung cancer
Approximately 250,000 patients are diagnosed with small cell lung cancer (SCLC) each year globally. There were approximately 27,000 new cases of SCLC in the U.S. in 2025, accounting for about 12% of all lung cancer cases. SCLC is aggressive and progresses rapidly to the distant metastatic stage, which has a low five-year survival rate. While conventional standard of care treatments for patients with advanced SCLC may help improve outcomes, there is a need for additional subsequent treatment approaches.
About B7-H3
B7-H3 is a transmembrane protein that belongs to the B7 family of proteins, which bind to the CD28 family of receptors that includes PD-1. B7-H3 is overexpressed in a wide range of cancer types, including SCLC, and its overexpression has been shown to correlate with poor prognosis, making B7-H3 a promising therapeutic target. There are currently no B7-H3 directed medicines approved for the treatment of cancer.
About ifinatamab deruxtecan
Ifinatamab deruxtecan is an investigational potential first-in-class B7-H3 directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, ifinatamab deruxtecan is comprised of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Ifinatamab deruxtecan was granted Breakthrough Therapy Designation by the FDA for the treatment of adult patients with ES-SCLC with disease progression on or after platinum-based chemotherapy.
Ifinatamab deruxtecan has been granted Orphan Drug Designation (ODD) by the U.S. FDA, European Commission, Japan Ministry of Health, Labour and Welfare and Taiwan Food and Drug Administration for the treatment of SCLC. Ifinatamab deruxtecan also was granted ODD for the treatment of esophageal cancer by the FDA.
About the ifinatamab deruxtecan clinical development program
A comprehensive global clinical development program is underway evaluating the efficacy and safety of ifinatamab deruxtecan monotherapy and in combination with other cancer medicines across multiple cancers. The program is currently comprised of three Phase 3 trials in advanced/metastatic disease, including SCLC (IDeate-Lung02), castration-resistant prostate cancer (IDeate-Prostate01) and esophageal squamous cell carcinoma (IDeate-Esophageal01).
About the Daiichi Sankyo and Merck collaboration
Daiichi Sankyo and Merck entered into a global collaboration in October 2023 to jointly develop and commercialize ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), except in Japan where Daiichi Sankyo will maintain exclusive rights. Daiichi Sankyo will be solely responsible for manufacturing and supply. In August 2024, the global co-development and co-commercialization agreement was expanded to include gocatamig (MK-6070/DS3280), which the companies will jointly develop and commercialize worldwide, except in Japan where Merck will maintain exclusive rights. Merck will be solely responsible for manufacturing and supply for gocatamig.
About the ADC portfolio of Daiichi Sankyo
The Daiichi Sankyo ADC portfolio consists of eight ADCs in clinical development crafted from ADC technology discovered in-house by Daiichi Sankyo.
The DXd ADC Technology platform of Daiichi Sankyo consists of seven ADCs in clinical development where each ADC is comprised of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The DXd ADCs include ENHERTU® and DATROWAY®, which are being jointly developed and commercialized globally with AstraZeneca, and ifinatamab deruxtecan (I-DXd), raludotatug deruxtecan (R-DXd) and patritumab deruxtecan (HER3-DXd), which are being jointly developed and commercialized globally with Merck. DS-3939 and DS3790 are being developed by Daiichi Sankyo.
An additional ADC being developed by Daiichi Sankyo is DS3610, which consists of an antibody attached to a novel payload that acts as an agonist of STING.
Ifinatamab deruxtecan, raludotatug deruxtecan, patritumab deruxtecan, DS-3939, DS3610 and DS3790 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
About Daiichi Sankyo
Daiichi Sankyo is an innovative global healthcare company contributing to the sustainable development of society that discovers, develops and delivers new standards of care to enrich the quality of life around the world. With more than 120 years of experience, Daiichi Sankyo leverages its world-class science and technology to create new modalities and innovative medicines for people with cancer, cardiovascular and other diseases with high unmet medical needs.
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