Advancing Care in Small Cell Lung Cancer: Optimizing Immunotherapy, Managing Toxicities, and Exploring Emerging Therapies - Episode 15
Intracranial Efficacy and Safety Findings in Patients with Baseline Brain Metastases
Dr. Dowlati reviews the primary results from IDeate-Lung01 as of the March 3, 2025 data cutoff. Among 137 patients treated with ifinatamab deruxtecan at 12 mg/kg, 65 (47%) had baseline brain metastases. Of these, 29 patients (45%) had measurable target lesions and 26 (40%) had not received prior brain radiation. The confirmed CNS objective response rate was 46.2% overall, increasing to 65.5% in patients with measurable target lesions and 57.7% among those without prior radiation, demonstrating meaningful intracranial activity even in untreated brain lesions. Safety outcomes were similar between patients with and without brain metastases, with grade 3 or higher treatment-related adverse events reported in 31% versus 42% of patients, respectively. Dr. Dowlati emphasizes that the presence of brain metastases did not increase toxicity risk with I-DXd treatment.
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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