The FDA has granted Breakthrough Therapy Designation to ifinatamab deruxtecan (I-DXd), the first B7-H3-directed antibody-drug conjugate, for patients with extensive-stage small cell lung cancer who have progressed on platinum-based chemotherapy. This designation accelerates development of a potentially transformative treatment for a patient population with extremely limited therapeutic options and poor prognosis.
Study Design & Population
- IDeate-Lung01: Global, multicenter, randomized, open-label phase 2 trial
- Sample size: 187 patients across Asia, Europe, and North America
- Patient population: Extensive-stage SCLC with 1-3 prior lines of therapy including platinum-based chemotherapy
- Key eligibility: Patients with asymptomatic brain metastases (treated or untreated) were eligible
- Dosing: Two-part study with dose optimization (8 vs 12 mg/kg) followed by expansion at 12 mg/kg IV Q3W
Key Findings
- Primary endpoint: Objective response rate (ORR) assessed by blinded independent central review per RECIST v1.1
- Supporting data: Additional evidence from IDeate-PanTumor01 phase 1/2 trial (~250 patients)
- Mechanism: First-in-class B7-H3-directed ADC using Daiichi Sankyo’s proprietary DXd technology
- Results presentation: Primary analysis data to be presented at IASLC 2025 World Conference on Lung Cancer
- Regulatory milestone: First BTD for ifinatamab deruxtecan and fourteenth BTD across Daiichi Sankyo’s oncology portfolio
Clinical Implications
- Addresses critical unmet need: SCLC accounts for ~15% of lung cancers with aggressive progression and low 5-year survival
- Novel target: B7-H3 is overexpressed across multiple cancer types and correlates with poor prognosis
- Treatment positioning: Potential new option for patients progressing after standard platinum-based therapy
- Development acceleration: BTD enables expedited FDA review process for this high-priority indication
Limitations
- Data pending: Specific efficacy and safety data from IDeate-Lung01 not yet publicly available
- Early development: Investigational agent with safety and efficacy not yet established
- Limited scope: Current designation specific to pretreated extensive-stage SCLC population
- Competition timeline: No approved B7-H3-directed therapies currently available for comparison
