Advancing Care in Small Cell Lung Cancer: Optimizing Immunotherapy, Managing Toxicities, and Exploring Emerging Therapies - Episode 16
Clinical Significance of Intracranial Activity and Comparison with Other Therapies
Dr. Dowlati contextualizes the IDeate-Lung01 findings by emphasizing how common brain metastases are in small cell lung cancer, affecting up to 80% of patients during the disease course. He praises the trial investigators for specifically evaluating intracranial outcomes, noting that ifinatamab deruxtecan demonstrated strong activity in the brain, with response rates above 50% even in patients who had not received prior radiation. This level of activity is comparable to systemic response rates seen with first-line chemotherapy and similar to results from other antibody–drug conjugates in development. Dr. Dowlati highlights that treatment with I-DXd did not lead to higher toxicity and achieved a 91% CNS disease control rate, a median intracranial response duration of 6.2 months, and a median time to response of 1.4 months. In patients without prior brain radiation, the CNS disease control rate was 92% with a median response duration of 6.7 months, supporting I-DXd’s potential as an effective and well-tolerated therapy for patients with and without prior brain-directed 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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