Tarlatamab Improves Intracranial Outcomes and May Overcome Poor Prognosis in Relapsed SCLC With Brain Metastases

In this interview with Pharmacy Times at the 2026 American Society of Clinical Oncology Annual Meeting, Giannis Mountzios, MD, MSc, PhD, medical oncologist at Henry Dunant Hospital Center in Athens, Greece, discusses findings from Abstract #8006 of the phase 3 DeLLphi-304 trial (NCT05740566) evaluating the intracranial efficacy of tarlatamab (IMDELLTRA; Amgen) compared with chemotherapy in patients receiving second-line treatment for small cell lung cancer (SCLC) who had brain metastases at baseline. Mountzios highlights that patients treated with tarlatamab achieved a median overall survival of 13.9 months despite the presence of brain metastases, a result comparable to patients without brain metastases, suggesting the therapy may help overcome the historically poor prognosis associated with central nervous system (CNS) involvement. He also reviews data showing significant improvements in CNS progression-free survival, with the median not reached in the tarlatamab arm versus 7.1 months with chemotherapy.

Pharmacy Times: Patients with brain metastases often have poor outcomes in relapsed SCLC. What is the key takeaway from these intracranial efficacy findings?

Giannis Mountzios, MD, MSc, PhD: The key takeaway from these intracranial efficacy data presented at ASCO 2026 is that treatment with tarlatamab has the potential to overcome the historically poor prognosis of patients with relapsed small cell lung cancer and baseline brain metastases. The data showed that the median overall survival among patients with baseline brain metastases treated with tarlatamab was 13.9 months, which was similar to the median overall survival observed in patients without brain metastases who were treated with tarlatamab. These findings suggest that tarlatamab may have the potential to mitigate the poor prognosis traditionally associated with brain metastases in patients with small cell lung cancer.

Pharmacy Times: How do the improvements in CNS progression-free survival and overall survival help support the use of tarlatamab in patients with brain metastases?

Mountzios: Please allow me to briefly review the intracranial efficacy data presented at ASCO 2026. First, in the overall intent-to-treat population, which included patients with and without baseline brain metastases, treatment with tarlatamab significantly improved median progression-free survival in the central nervous system. Median CNS progression-free survival was not reached in the tarlatamab arm compared with 7.1 months in the standard chemotherapy arm. This result was highly statistically significant, with a hazard ratio of 0.54, suggesting that treatment with tarlatamab reduced the risk of CNS progression by approximately 46%.

Of note, when the analysis was restricted to patients with baseline brain metastases, and further limited to those with at least 1 confirmed brain metastasis according to modified RANO-BM criteria and at least 1 postbaseline brain scan available, treatment with tarlatamab significantly improved all intracranial efficacy outcomes. These included CNS complete response rates (15% vs 5%), median duration of complete response in the CNS, median duration of disease control in the CNS, and intracranial objective response rates. Intracranial objective response was defined as at least a 30% reduction in tumor size in at least 1 brain lesion measuring 10 mm or greater and evaluable for response.

Collectively, these data suggest that treatment with tarlatamab significantly improves intracranial efficacy outcomes related to brain metastases compared with chemotherapy in patients with relapsed small cell lung cancer.