Advancing Care in Small Cell Lung Cancer: Optimizing Immunotherapy, Managing Toxicities, and Exploring Emerging Therapies - Episode 14
Study Overview and Design of IDeate-Lung01: Evaluating I-DXd in ES-SCLC with Brain Metastases
Dr. Afshin Dowlati introduces the discussion by outlining the phase 2 IDeate-Lung01 trial, which evaluated ifinatamab deruxtecan (I-DXd) in patients with extensive-stage small cell lung cancer who had baseline brain metastases. He explains that the study began with a dose-escalation phase followed by dose expansion, during which patients received either 8 mg/kg or 12 mg/kg intravenously every three weeks. The final dosing selected for the expansion cohort was 12 mg/kg every three weeks. Dr. Dowlati details the imaging schedule, noting that all patients underwent baseline brain scans and those with brain metastases received follow-up MRIs every six weeks for 36 weeks and then every 12 weeks. Central nervous system responses were assessed using RECIST 1.1 criteria modified for brain tumor evaluation.
This program spotlights new data from the phase 2 IDeate-Lung01 trial evaluating ifinatamab deruxtecan (I-DXd), a B7-H3–directed antibody–drug conjugate, in patients with extensive-stage small cell lung cancer (ES-SCLC) and baseline brain metastases. Findings presented at ESMO 2025 highlight I-DXd’s potential to address the significant unmet need for effective central nervous system (CNS) therapy in this population.
Among 65 patients with baseline brain metastases, the CNS objective response rate (ORR) was 46% overall, increasing to 66% in those with measurable target lesions and 58% in patients who had not received prior brain radiation. Approximately one-third of patients achieved a complete response, and the CNS disease-control rate reached 91%. The median duration of intracranial response was 6.2 months, and the median time to response was 1.4 months—indicating both rapid onset and clinically meaningful durability of effect. Compared with agents such as topotecan or lurbinectedin, I-DXd demonstrated superior CNS activity in a heavily pretreated setting.
Safety results were consistent regardless of CNS involvement. Grade ≥3 treatment-related adverse events occurred in 31% of patients with brain metastases versus 42% without, and interstitial lung disease occurred in 11% versus 17%, respectively. No new neurologic or CNS-specific toxicities were reported, underscoring I-DXd’s manageable tolerability.
The discussion emphasizes how these results could inform future treatment sequencing, particularly regarding whether I-DXd should be considered earlier in therapy or in conjunction with radiation approaches. The forthcoming phase 3 IDeate-Lung02 trial will further evaluate intracranial outcomes, including CNS progression-free survival. Collectively, the IDeate-Lung01 findings suggest that I-DXd may represent a promising systemic option for patients with ES-SCLC and brain metastases, offering clinically meaningful responses where therapeutic options remain limited.
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