FDA Grants Priority Review to I-DXd in Advanced SCLC

The US FDA has accepted for priority review the biologics license application (BLA) for ifinatamab deruxtecan (I-DXd) for the treatment of adult patients with previously treated extensive-stage small cell lung cancer (ES-SCLC).¹ This regulatory milestone applies specifically to patients who have experienced disease progression on or after platinum-based chemotherapy. The FDA has set a Prescription Drug User Fee Act (PDUFA) date for October 10, 2026.

I-DXd is a potential first-in-class B7-H3–directed antibody-drug conjugate (ADC). The BLA is supported by clinical data from the phase 2 IDEATE-Lung01 (NCT05280470), which evaluated the efficacy and safety of the compound in patients with SCLC who had received at least 1 prior line of therapy.

“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 of Research and Develoopment, Daiichi Sankyo, in a news release.¹ “We look forward to continuing to work with the FDA to bring this potential first-in-class B7-H3–directed DXd antibody drug conjugate to patients as quickly as possible.”

Clinical Background and Mechanism of Action

SCLC remains one of the most aggressive forms of thoracic malignancy, characterized by rapid doubling time and early development of widespread metastases. While initial response rates to frontline platinum-based chemotherapy and immune checkpoint inhibitors are often high, the majority of patients experience relapse within months.² For those who progress, second-line options are limited and often provide only modest survival benefits.

I-DXd utilizes Daiichi Sankyo’s proprietary DXd ADC technology. It consists of a humanized anti-B7-H3 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker.¹

B7-H3, a member of the B7 family of immune checkpoint proteins, is highly expressed in SCLC and several other solid tumors, while maintaining low expression in normal tissues. This expression pattern makes it a viable target for ADC-mediated delivery of cytotoxic agents directly to the tumor microenvironment

Evidence from the IDEATE-Lung01 Trial

The priority review status is largely predicated on the results of the IDEATE-Lung01 study. This global, multicenter, randomized phase 2 trial assessed 2 different dose levels of I-DXd (8.0 mg/kg and 12.0 mg/kg) in patients with ES-SCLC.

Preliminary data presented at the 2025 ESMO Congress indicated that I-DXd demonstrated a clinically meaningful objective response rate (ORR) in patients who had previously failed platinum-based chemotherapy. The durability of these responses is a key focus of the ongoing regulatory assessment.³

The safety profile of I-DXd was consistent with previous observations in the [hase 1/2 study (NCT04145622).⁴ Common treatment-emergent adverse events included nausea, fatigue, and hematologic toxicities. Notably, clinicians are monitoring for interstitial lung disease (ILD) and pneumonitis, which are known risks associated with the DXd ADC platform. In clinical trials, most ILD events were low grade.

REFERENCES

1. Ifinatamab Deruxtecan Granted Priority Review in the U.S. for Adult Patients with Previously Treated Extensive-Stage Small Cell Lung Cancer who Experienced Disease Progression on or After Platinum-Based Chemotherapy. News release. Daiichi Sankyo. April 13, 2026. Accessed April 13, 2026. https://tinyurl.com/yyk2vva4

2. Lung Cancer Survival Rates. American Cancer Society. Updated January 2024. Accessed April 13, 2026. https://tinyurl.com/mwwazhpv

2. Rudin CM, Johnson ML, Paz-Ares L, et al. Ifinatamab Deruxtecan in Patients With Extensive-Stage Small Cell Lung Cancer: Primary Analysis of the Phase II IDeate-Lung01 Trial. J Clin Oncol. 2026 Feb;44(4):261-273. doi: 10.1200/JCO-25-02142. Epub 2025 Oct 14. PMID: 41086386; PMCID: PMC12834294.

4. Bendell J, Doi T, Patel MR, et al. A phase I/II, two-part, multicenter, first-in-human study of DS-7300a in patients with advanced solid malignant tumors. J Clin Oncol. 38, TPS3646-TPS3646(2020). doi:10.1200/JCO.2020.38.15_suppl.TPS3646