Ifinatamab Deruxtecan (previously known as DS-7300a), a B7-H3-directed antibody-drug conjugate being developed by Daiichi Sankyo and Merck & Co. (known as MSD outside of the United States and Canada), could offer a First-in-Class option for patients diagnosed with extensive-stage small cell lung cancer (ES-SCLC) following platinum-based chemotherapy.
Following the application, the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to the Biologics License Application (BLA) for ifinatamab deruxtecan (I-DXd) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) who have experienced disease progression on or after platinum-based chemotherapy. If approved, ifinatamab deruxtecan would represent the first B7-H3-directed DXd antibody-drug conjugate (ADC) available for this patient population.
The Priority Review designation is based on results from the pivotal phase 2 IDeate-Lung01 trial, with additional support from the phase 1/2 IDeate-PanTumor01 trial. The FDA also granted the application Real-Time Oncology Review (RTOR) and Project Orbis status, both designed to accelerate the availability of novel cancer therapies. The Prescription Drug User Fee Act (PDUFA) action date for a regulatory decision is set for October 10, 2026.
An Unmet Need in Small Cell Lung Cancer
Small cell lung cancer is an aggressive malignancy that accounts for approximately 12% of all lung cancer diagnoses, with around 27,000 new cases annually in the United States.[1][2][3][4] Globally, SCLC affects about 250,000 patients each year. [5] The disease is characterized by rapid progression, early metastasis, and poor prognosis, especially in patients with extensive-stage disease. [6][7]While initial responses to platinum-based chemotherapy are common, most patients relapse, and effective subsequent treatment options remain limited.[8][9][10][11]
B7-H3 as a Therapeutic Target
B7-H3 is an immune checkpoint protein of the B7 family that is overexpressed in a variety of solid tumors, including SCLC.[12][13] Its presence is associated with poor clinical outcomes, making it a promising therapeutic target. Although there are currently no B7-H3-directed agents approved for cancer treatment, this immune checkpoint protein has attracted attention from drug developers because of its expression in immune ‘cold’ tumors, in which PD-1 and PD-L1 are minimally expressed, making these tumors unresponsive to most currently used immunotherapies. Being an interesting target also means that drug developers are exploring the opportunities in targeting B7-HV. This, in turn, has resulted in a crowded field of multiple development initiatives, some ongoing, and some canceled.[14][15[16][17]
For example, in February 2025, Pfizer discontinued development of felmetatug vedotin (SGN-B7H4V / PF-08046048), a B7-H4-directed ADC that used a monomethyl auristatin E (MMAE; vedotin) payload. AstraZeneca’s B7-H4 ADC, puxitatug samrotecan (AZD0205), is currently in Phase 3 clinical studies, while NextCure’s LNCB74, another B7-H4-targeting ADC, is being co-developed with LigaChem Biosciences. Emiltatug ledadotin (XMT-1660), an investigational Dolasynthen B7-H4-targeted ADC being developed by Day One biopharmaceuticals*, is currently in Phase 1 trials for solid tumors, while Mocertatug rezetecan, a novel ADC being developed by GSK and Hansoh Pharma, combines a humanized anti-B7-H4 monoclonal antibody with an exatecan-derived topoisomerase I inhibitor payload (SHR-9265; average drug-to-antibody ratio [DAR] of 6). Finally, BG-C9074 is an investigational topoisomerase I inhibitor ADC being developed by BeOne Medicines **
A targeted agent
Ifinatamab deruxtecan is an investigational ADC comprising a humanized anti-B7-H3 IgG1 monoclonal antibody conjugated via a cleavable tetrapeptide linker to a topoisomerase I inhibitor payload (DXd, an exatecan derivative). The drug was developed using Daiichi Sankyo’s proprietary DXd ADC technology and is the first ADC designed to target B7-H3, aiming to selectively deliver cytotoxic chemotherapy to B7-H3-expressing tumor cells.
Ifinatamab deruxtecan previously received Breakthrough Therapy Designation from the FDA in August 2025 for the treatment of adult patients with ES-SCLC following progression on platinum-based chemotherapy. Orphan Drug Designation has also been granted by regulatory agencies in the U.S., Europe, Japan, and Taiwan for SCLC, as well as for esophageal cancer in the U.S.
Clinical Evidence Supporting the Application
The BLA submission is supported primarily by the IDeate-Lung01 phase 2 trial, a global, multicenter, randomized, open-label study enrolling 187 patients with ES-SCLC who had received at least one prior line of platinum-based chemotherapy (and up to three prior lines of therapy). The trial allowed enrollment of patients with asymptomatic brain metastases. In the dose optimization phase, patients were randomized to receive ifinatamab deruxtecan at 8 or 12 mg/kg IV every three weeks, followed by a dose expansion phase at 12 mg/kg.
The primary endpoint was objective response rate (ORR) as assessed by blinded independent central review 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 response was assessed as an exploratory endpoint.
Data from IDeate-Lung01, presented at the 2025 World Conference on Lung Cancer and published in the Journal of Clinical Oncology, demonstrated clinically meaningful anti-tumor activity and a manageable safety profile in this heavily pretreated population. The supportive IDeate-PanTumor01 phase 1/2 trial further established the safety and efficacy of ifinatamab deruxtecan across multiple advanced solid tumors.
Ongoing Clinical Development
Ifinatamab deruxtecan is being evaluated in a comprehensive global clinical development program, including phase 3 trials in SCLC (IDeate-Lung02), metastatic castration-resistant prostate cancer (IDeate-Prostate01), and esophageal squamous cell carcinoma (IDeate-Esophageal01).
Expert Commentary
“The FDA’s granting of Priority Review for ifinatamab deruxtecan marks a significant milestone in our effort to provide new and innovative treatment options for patients with extensive-stage small cell lung cancer,” said John Tsai, MD, Global Head, R&D, Daiichi Sankyo.
“We look forward to working with the FDA to potentially bring this first-in-class B7-H3 directed ADC to patients as quickly as possible.”
Eliav Barr, MD, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, MSD Research Laboratories, added, “Small cell lung cancer remains one of the toughest cancers to treat, with few options if the disease progresses after standard of care treatments. The FDA’s acceptance of the BLA reinforces the important role that ifinatamab deruxtecan could play in helping to address the needs of patients with extensive-stage small cell lung cancer.”
What’s next
If approved, ifinatamab deruxtecan would become the first B7-H3 directed ADC for adult patients with previously treated ES-SCLC, potentially addressing a critical gap in therapy for this aggressive cancer. The Priority Review, Breakthrough Therapy, and Orphan Drug designations highlight the urgency and promise of this innovative approach.
Note:* Day One Biopharmaceuticals completed its acquisition of Mersana Therapeutics on January 6, 2026, for US $25 per share in cash, plus contingent value rights (CVRs) potentially totaling US $285 million. The deal, which makes Mersana Therapeutics a wholly owned subsidiary, adds the ADC candidate Emi-Le (emiltatug ledadotin) to Day One’s portfolio.
** In December 2024, BeiGene in-licensed DB 1312 (BG-C9074) from Duality Biologics.
Clinical trials
Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) (IDeate-Lung01) – ClinicalTrials.gov ID NCT05280470
Study of Ifinatamab Deruxtecan (DS-7300a, I-DXd) in Participants With Advanced Solid Malignant Tumors – ClinicalTrials.gov ID NCT04145622
Reference
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DOI: 10.14229/jadc.2026.13.04.009
