Ifinatamab Deruxtecan Granted Priority Review for Previously Treated Extensive-Stage Small Cell Lung Cancer

The FDA has accepted and granted Priority Review to a biologics license application (BLA) for ifinatamab deruxtecan (I-DXd) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease has progressed on or after platinum-based chemotherapy.

The agency has set a Prescription Drug User Fee Act target action date of October 10, 2026.

If approved, the investigational therapy—jointly developed by Daiichi Sankyo

and Merck—would represent a potential first-in-class B7-H3–directed antibody-drug conjugate (ADC) for this patient population, which currently faces limited treatment options and poor prognosis.

Clinical evidence supports submission

The BLA is primarily supported by data from the global Phase 2 IDeate-Lung01 trial,¹ with additional evidence from the Phase 1/2 IDeate-PanTumor01 study.²

In IDeate-Lung01, I-DXd demonstrated clinically meaningful antitumor activity in heavily pretreated ES-SCLC patients. At the 12 mg/kg dose, the therapy achieved an objective response rate (ORR) of 48.2%, with a median duration of response of 5.3 months and median progression-free survival of 4.9 months.

The trial enrolled 187 patients globally and evaluated intravenous dosing every three weeks. The primary endpoint was ORR as assessed by blinded independent central review, with secondary endpoints including overall survival (OS), duration of response, and safety.

In IDeate-PanTumor01, I-DXd continued to demonstrate a manageable safety profile and promising antitumor activity with encouraging duration of response and OS in heavily pretreated patients with advanced solid tumors.

This study recruited 97 patients aged 18 years or older in the US and Japan who had advanced treatment-refractory solid tumors (small-cell lung cancer, esophageal squamous cell carcinoma, castration-resistant prostate cancer, squamous non-small-cell lung cancer, head and neck squamous cell carcinoma, bladder cancer, sarcoma, endometrial cancer, melanoma, or breast cancer).

Patients received I-DXd at doses of 0·8–16·0 mg/kg intravenously every 3 weeks. The primary outcome of dose escalation was the safety profile, which was evaluated in patients who received one or more dose of I-DXd. Antitumor activity was evaluated in patients receiving I-DXd at doses of 4.8 mg/kg or higher. 

Regulatory pathways aim to accelerate review

In addition to Priority Review, the application is being evaluated under the FDA’s Real-Time Oncology Review program and Project Orbis, initiatives designed to expedite development and enable concurrent international regulatory review.

The therapy previously received Breakthrough Therapy Designation in 2025 for the same indication, underscoring its potential to address a significant unmet need.

Addressing a substantial unmet need

Small cell lung cancer is an aggressive malignancy characterized by rapid progression and high rates of metastasis. Approximately 250,000 cases are diagnosed globally each year, and outcomes remain poor, particularly after progression on first-line platinum-based chemotherapy.

I-DXd targets B7-H3, a protein overexpressed across multiple tumor types and associated with poor prognosis. No therapies directed at B7-H3 are currently approved, positioning the ADC as a novel mechanism of action in this setting.

Ongoing development

A broader clinical development program is underway to evaluate I-DXd across multiple tumor types, including Phase 3 trials in small cell lung cancer, castration-resistant prostate cancer, and esophageal squamous cell carcinoma.

If approved, the therapy could expand the treatment landscape for patients with relapsed ES-SCLC and mark an important milestone in the advancement of targeted ADC technologies in oncology.

References:

1. Rudin, C. M., et al. (2025, October 14). Ifinatamab deruxtecan in patients with extensive-stage small cell lung cancer: Primary analysis of the phase II IDeate-Lung01 trial. Journal of Clinical Oncology. https://doi.org/10.1200/JCO-25-02142
   
2. Johnson, M.L., et al. (2026, April). Ifinatamab deruxtecan, a B7-H3-directed antibody–drug conjugate, in patients with advanced solid tumours (IDeate-PanTumor01): dose-escalation results from a phase 1/2 trial. The Lancet. https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(25)00733-8/abstract